CBD was predicted to precipitate strong drug interactions (AUCR greater than or equal to 5) mediated by CYP2C9, 2C19, and 3A and moderate drug interactions (AUCR between 1.2 and 5) mediated by CYP1A2 and 2D6 based on the AUCR cutoffs recommended by the FDA (https://www.fda.gov/media/134582/ download).
\nTable 1 lists the oral and inhalational doses and estimated maximum plasma concentrations of CBD, THC, and THC metabolites used for predicting the magnitude of pharmacokinetic cannabinoid-drug interactions.
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The binding-corrected reversible (IC50,u) and irreversible inhibition potency (KI,u) values were determined for CBD and THC. A combined mechanistic static model showed a moderate-strong interaction between CBD and drugs metabolized via CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A. The model also showed an interaction between THC and CYP1A2, CYP2C9, and CYP3A.","study.pubmedId":32587099,"study.embaseId":null,"study.croIdentifier":"UW-WSU-NaPDI","study.croInformation":"Department of Pharmaceutics, UW; Department of Pharmaceutical Sciences, WSU; NaPDI","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis 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\nTable 1 lists the oral and inhalational doses and estimated maximum plasma concentrations of CBD, THC, and THC metabolites used for predicting the magnitude of pharmacokinetic cannabinoid-drug interactions.
","croIdentifier":"UW-WSU-NaPDI-CBD-CYP2D6","comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":12,"objectMetaboliteCompoundId":13,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":787,"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":115,"precipitantCompound.name":"cannabidiol","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"QHMBSVQNZZTUGM-ZWKOTPCHSA-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":1110,"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":787,"study.uid":"NPDI-lalKkg","study.name":"Predicting the Potential for Cannabinoids to Precipitate Pharmacokinetic Drug Interactions via Reversible Inhibition or Inactivation of Major Cytochromes P450","study.napdiIdentifier":null,"study.overallSummary":"Cannabis constituents, CBD and THC, have been known to inhibit or inactive CYP450 enzymes. 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\nTable 1 lists the oral and inhalational doses and estimated maximum plasma concentrations of CBD, THC, and THC metabolites used for predicting the magnitude of pharmacokinetic cannabinoid-drug interactions.
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\nTable 1 lists the oral and inhalational doses and estimated maximum plasma concentrations of CBD, THC, and THC metabolites used for predicting the magnitude of pharmacokinetic cannabinoid-drug interactions.
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