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[<em>K<sub>i</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression and competitive inhibition model.]</span></div>","internalComment":null,"objectCompoundId":12,"objectMetaboliteCompoundId":13,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":6,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":12,"objectCompound.name":"dextromethorphan","objectCompound.unii":"7355X3ROTS","objectCompound.inChIKey":"MKXZASYAUGDDCJ-NJAFHUGGSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":1119510,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":1119510,"objectCompound.concept.conceptName":"Dextromethorphan","objectCompound.concept.domainId":"Drug","objectCompound.concept.vocabularyId":"RxNorm","objectCompound.concept.conceptClassId":"Ingredient","objectCompound.concept.standardConcept":"S","objectCompound.concept.conceptCode":"3289","objectCompound.concept.validStartDate":"1970-01-01T00:00:00.000Z","objectCompound.concept.validEndDate":"2099-12-31T00:00:00.000Z","objectCompound.concept.invalid_reason":null,"precipitantCompound.id":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":13,"objectMetaboliteCompound.name":"dextrorphan","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"JAQUASYNZVUNQP-PVAVHDDUSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":4349487,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":4349487,"objectMetaboliteCompound.concept.conceptName":"Dextrorphan","objectMetaboliteCompound.concept.domainId":"Drug","objectMetaboliteCompound.concept.vocabularyId":"NDFRT","objectMetaboliteCompound.concept.conceptClassId":"Chemical Structure","objectMetaboliteCompound.concept.standardConcept":"C","objectMetaboliteCompound.concept.conceptCode":"N0000167299","objectMetaboliteCompound.concept.validStartDate":"1970-01-01T00:00:00.000Z","objectMetaboliteCompound.concept.validEndDate":"2099-12-31T00:00:00.000Z","objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":10,"enzymes.name":"CYP2D6","enzymes.conceptId":4173631,"enzymes.experiment_enzyme_xref.enzymeId":10,"enzymes.experiment_enzyme_xref.experimentId":694,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":143,"study.uid":"NPDI-d8OUzg","study.name":"Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations","study.napdiIdentifier":null,"study.overallSummary":"<ul>\r\n<li><span lang=\"EN-US\">All kratom extracts inhibited CYP2C9, CYP2D6 and CYP3A (hepatic and intestinal) activities by similar extents, indicating minimal product to product variability with respect to CYP inhibition. Mitragynine inhibited CYP2C9, CYP2D6, and CYP3A activity by greater than 50%, warranting further investigation as a reversible or a time dependent inhibitor of the CYP activities.</span></li>\r\n<li><span lang=\"EN-US\">The 7-fold shift observed with mitragynine against intestinal and hepatic CYP3A activity suggests mitragynine is a time dependent inhibitor. IC<sub>50</sub>values were within the concentration range reported in post-mortem human plasma and tissues. Although no leftward shift was observed for CYP2D6, the IC<sub>50</sub>was also within the concentration range reported in post-mortem human plasma and tissues.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine was shown to be a strong competitive inhibitor of CYP2D6 activity. 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The kinetic parameters, <em>K<sub>I</sub></em>and <em>k<sub>inact</sub></em>will be applied to mechanistic and PBPK models to predict drug interaction potential.<br /></span></li>\r\n</ul>","study.pubmedId":33093187,"study.embaseId":null,"study.croIdentifier":"Washington State University","study.croInformation":"Washington State University","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Data entered by CB and review by RB.","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":"NPS-oDLatA","study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna 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Quinidine (2 µM) served as positive control inhibitors of CYP2D6 activity.</span></div>","resultsComment":"<div><span lang=\"EN-US\">Mitragynine was shown to be a strong competitive inhibitor of CYP2D6 activity, with a <em>K<sub>i</sub></em>of 0.97  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">0.07 µM, 1.25  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">0.09 µM, and 0.95 </span><span lang=\"EN-US\">±  </span><span lang=\"EN-US\">0.11 µM, respectively, for three individual experiments. [<em>K<sub>i</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression and competitive inhibition model.]</span></div>","internalComment":null,"objectCompoundId":12,"objectMetaboliteCompoundId":13,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":6,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":12,"objectCompound.name":"dextromethorphan","objectCompound.unii":"7355X3ROTS","objectCompound.inChIKey":"MKXZASYAUGDDCJ-NJAFHUGGSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":1119510,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":1119510,"objectCompound.concept.conceptName":"Dextromethorphan","objectCompound.concept.domainId":"Drug","objectCompound.concept.vocabularyId":"RxNorm","objectCompound.concept.conceptClassId":"Ingredient","objectCompound.concept.standardConcept":"S","objectCompound.concept.conceptCode":"3289","objectCompound.concept.validStartDate":"1970-01-01T00:00:00.000Z","objectCompound.concept.validEndDate":"2099-12-31T00:00:00.000Z","objectCompound.concept.invalid_reason":null,"precipitantCompound.id":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":13,"objectMetaboliteCompound.name":"dextrorphan","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"JAQUASYNZVUNQP-PVAVHDDUSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":4349487,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":4349487,"objectMetaboliteCompound.concept.conceptName":"Dextrorphan","objectMetaboliteCompound.concept.domainId":"Drug","objectMetaboliteCompound.concept.vocabularyId":"NDFRT","objectMetaboliteCompound.concept.conceptClassId":"Chemical Structure","objectMetaboliteCompound.concept.standardConcept":"C","objectMetaboliteCompound.concept.conceptCode":"N0000167299","objectMetaboliteCompound.concept.validStartDate":"1970-01-01T00:00:00.000Z","objectMetaboliteCompound.concept.validEndDate":"2099-12-31T00:00:00.000Z","objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":10,"enzymes.name":"CYP2D6","enzymes.conceptId":4173631,"enzymes.experiment_enzyme_xref.enzymeId":10,"enzymes.experiment_enzyme_xref.experimentId":694,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":143,"study.uid":"NPDI-d8OUzg","study.name":"Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations","study.napdiIdentifier":null,"study.overallSummary":"<ul>\r\n<li><span lang=\"EN-US\">All kratom extracts inhibited CYP2C9, CYP2D6 and CYP3A (hepatic and intestinal) activities by similar extents, indicating minimal product to product variability with respect to CYP inhibition. Mitragynine inhibited CYP2C9, CYP2D6, and CYP3A activity by greater than 50%, warranting further investigation as a reversible or a time dependent inhibitor of the CYP activities.</span></li>\r\n<li><span lang=\"EN-US\">The 7-fold shift observed with mitragynine against intestinal and hepatic CYP3A activity suggests mitragynine is a time dependent inhibitor. IC<sub>50</sub>values were within the concentration range reported in post-mortem human plasma and tissues. Although no leftward shift was observed for CYP2D6, the IC<sub>50</sub>was also within the concentration range reported in post-mortem human plasma and tissues.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine was shown to be a strong competitive inhibitor of CYP2D6 activity. 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The kinetic parameters, <em>K<sub>I</sub></em>and <em>k<sub>inact</sub></em>will be applied to mechanistic and PBPK models to predict drug interaction potential.<br /></span></li>\r\n</ul>","study.pubmedId":33093187,"study.embaseId":null,"study.croIdentifier":"Washington State University","study.croInformation":"Washington State University","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Data entered by CB and review by RB.","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":"NPS-oDLatA","study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna 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