[{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"
IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published 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available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10667,"experimentAnswers.text":"120 min","experimentAnswers.answerId":null,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":6,"experimentAnswers.question.id":6,"experimentAnswers.question.text":"Incubation time","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published 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available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10666,"experimentAnswers.text":"250 μL","experimentAnswers.answerId":null,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":5,"experimentAnswers.question.id":5,"experimentAnswers.question.text":"Incubation volume","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
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μM","experimentAnswers.answerId":null,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":15,"experimentAnswers.question.id":15,"experimentAnswers.question.text":"Precipitant concentrations tested","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10664,"experimentAnswers.text":"200 μg/incubation","experimentAnswers.answerId":null,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":2,"experimentAnswers.question.id":2,"experimentAnswers.question.text":"Protein concentration","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10663,"experimentAnswers.text":"100 μM","experimentAnswers.answerId":null,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":11,"experimentAnswers.question.id":11,"experimentAnswers.question.text":"Object concentrations tested","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published 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available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10662,"experimentAnswers.text":null,"experimentAnswers.answerId":15,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":10,"experimentAnswers.question.id":10,"experimentAnswers.question.text":"Time linearity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":15,"experimentAnswers.question.answers.text":"Not available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":10,"experimentAnswers.answer.id":15,"experimentAnswers.answer.text":"Not available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":10},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10662,"experimentAnswers.text":null,"experimentAnswers.answerId":15,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":10,"experimentAnswers.question.id":10,"experimentAnswers.question.text":"Time linearity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":14,"experimentAnswers.question.answers.text":"Available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":10,"experimentAnswers.answer.id":15,"experimentAnswers.answer.text":"Not available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":10},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10661,"experimentAnswers.text":null,"experimentAnswers.answerId":13,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":9,"experimentAnswers.question.id":9,"experimentAnswers.question.text":"Protein linearity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":13,"experimentAnswers.question.answers.text":"Not available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":9,"experimentAnswers.answer.id":13,"experimentAnswers.answer.text":"Not available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":9},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published 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available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10661,"experimentAnswers.text":null,"experimentAnswers.answerId":13,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":9,"experimentAnswers.question.id":9,"experimentAnswers.question.text":"Protein linearity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":12,"experimentAnswers.question.answers.text":"Available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":9,"experimentAnswers.answer.id":13,"experimentAnswers.answer.text":"Not available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":9},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10660,"experimentAnswers.text":null,"experimentAnswers.answerId":9,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":8,"experimentAnswers.question.id":8,"experimentAnswers.question.text":"Co-substrate","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":11,"experimentAnswers.question.answers.text":"GSH","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":8,"experimentAnswers.answer.id":9,"experimentAnswers.answer.text":"UDPGA","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":8},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10660,"experimentAnswers.text":null,"experimentAnswers.answerId":9,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":8,"experimentAnswers.question.id":8,"experimentAnswers.question.text":"Co-substrate","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":10,"experimentAnswers.question.answers.text":"PAPS","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":8,"experimentAnswers.answer.id":9,"experimentAnswers.answer.text":"UDPGA","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":8},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published 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available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10660,"experimentAnswers.text":null,"experimentAnswers.answerId":9,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":8,"experimentAnswers.question.id":8,"experimentAnswers.question.text":"Co-substrate","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":9,"experimentAnswers.question.answers.text":"UDPGA","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":8,"experimentAnswers.answer.id":9,"experimentAnswers.answer.text":"UDPGA","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":8},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10659,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":8,"experimentAnswers.question.answers.text":"P450 reductase","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10659,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":7,"experimentAnswers.question.answers.text":"NADPH regenerating system","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published 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available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10659,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":6,"experimentAnswers.question.answers.text":"NADPH","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10659,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":5,"experimentAnswers.question.answers.text":"NADH","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10659,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":4,"experimentAnswers.question.answers.text":"NAD","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published 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available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10659,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":583,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":3,"experimentAnswers.question.answers.text":"MgCl2","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":583,"uid":"NPDI-5VhYlA","name":"Negligible inhibition of UGT1A1 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"IC50 > 10 μM are low potential inhibitors.
1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna 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1 μM < IC50 < 10 μM are moderate potential inhibitors.
IC50 < 1 μM are high potential inhibitors.
Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
\r\nObjective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
\r\nMaterials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
\r\nResults: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
\r\nConclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
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