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and 0.17  </span><span lang=\"EN-US\">± 0.02 min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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served as a positive control inhibitor of CYP3A activity.</span></div>","resultsComment":"<div><span lang=\"EN-US\">The <em>K<sub>I</sub></em>and <em>k<sub>inact</sub></em>values for mitragynine towards CYP3A activity in HIM were 4.5  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">1.1 µM and 0.072  </span><span lang=\"EN-US\">± 0.006 min-<sup>1</sup>,  </span><span lang=\"EN-US\">6.0  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">0.5 µM and 0.074  </span><span lang=\"EN-US\">± 0.002 min-<sup>1</sup>, and  </span><span lang=\"EN-US\">7.3  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">2.5 µM and 0.17  </span><span lang=\"EN-US\">± 0.02 min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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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min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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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lang=\"EN-US\">± </span><span lang=\"EN-US\">1.1 µM and 0.072  </span><span lang=\"EN-US\">± 0.006 min-<sup>1</sup>,  </span><span lang=\"EN-US\">6.0  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">0.5 µM and 0.074  </span><span lang=\"EN-US\">± 0.002 min-<sup>1</sup>, and  </span><span lang=\"EN-US\">7.3  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">2.5 µM and 0.17  </span><span lang=\"EN-US\">± 0.02 min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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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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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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- 30 µM","experimentAnswers.answerId":null,"experimentAnswers.experimentId":696,"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":696,"uid":"NPDI-Tr3Eyg","name":"Inhibition kinetics of CYP3A activity by mitragynine in 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three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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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regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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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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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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pre-incubation condition","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":26,"experimentAnswers.question.answers.text":"No NADPH with no precipitant","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":22,"experimentAnswers.answer.id":23,"experimentAnswers.answer.text":"NADPH with precipitant","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":22},{"id":696,"uid":"NPDI-Tr3Eyg","name":"Inhibition kinetics of CYP3A activity by mitragynine in HIM","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>N/A</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"<div><span lang=\"EN-US\">Methanol (0.8 % v/v) served as solvent control. 6',7'-Dihydroxybergamottin (1 and 2 µM) served as a positive control inhibitor of CYP3A activity.</span></div>","resultsComment":"<div><span lang=\"EN-US\">The <em>K<sub>I</sub></em>and <em>k<sub>inact</sub></em>values for mitragynine towards CYP3A activity in HIM were 4.5  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">1.1 µM and 0.072  </span><span lang=\"EN-US\">± 0.006 min-<sup>1</sup>,  </span><span lang=\"EN-US\">6.0  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">0.5 µM and 0.074  </span><span lang=\"EN-US\">± 0.002 min-<sup>1</sup>, and  </span><span lang=\"EN-US\">7.3  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">2.5 µM and 0.17  </span><span lang=\"EN-US\">± 0.02 min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"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":26,"objectCompound.name":"midazolam","objectCompound.unii":"R60L0SM5BC","objectCompound.inChIKey":"DDLIGBOFAVUZHB-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":708298,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":708298,"objectCompound.concept.conceptName":"Midazolam","objectCompound.concept.domainId":"Drug","objectCompound.concept.vocabularyId":"RxNorm","objectCompound.concept.conceptClassId":"Ingredient","objectCompound.concept.standardConcept":"S","objectCompound.concept.conceptCode":"6960","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":1,"objectMetaboliteCompound.name":"1'-hydroxymidazolam","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"QHSMEGADRFZVNE-UHFFFAOYSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":30,"enzymes.name":"CYP3A","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":30,"enzymes.experiment_enzyme_xref.experimentId":696,"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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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pre-incubation condition","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":25,"experimentAnswers.question.answers.text":"No NADPH with precipitant","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":22,"experimentAnswers.answer.id":23,"experimentAnswers.answer.text":"NADPH with precipitant","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":22},{"id":696,"uid":"NPDI-Tr3Eyg","name":"Inhibition kinetics of CYP3A activity by mitragynine in HIM","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>N/A</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"<div><span lang=\"EN-US\">Methanol (0.8 % v/v) served as solvent control. 6',7'-Dihydroxybergamottin (1 and 2 µM) served as a positive control inhibitor of CYP3A activity.</span></div>","resultsComment":"<div><span lang=\"EN-US\">The <em>K<sub>I</sub></em>and <em>k<sub>inact</sub></em>values for mitragynine towards CYP3A activity in HIM were 4.5  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">1.1 µM and 0.072  </span><span lang=\"EN-US\">± 0.006 min-<sup>1</sup>,  </span><span lang=\"EN-US\">6.0  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">0.5 µM and 0.074  </span><span lang=\"EN-US\">± 0.002 min-<sup>1</sup>, and  </span><span lang=\"EN-US\">7.3  </span><span lang=\"EN-US\">± </span><span lang=\"EN-US\">2.5 µM and 0.17  </span><span lang=\"EN-US\">± 0.02 min-<sup>1</sup>, respectively, for three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"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":26,"objectCompound.name":"midazolam","objectCompound.unii":"R60L0SM5BC","objectCompound.inChIKey":"DDLIGBOFAVUZHB-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":708298,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":708298,"objectCompound.concept.conceptName":"Midazolam","objectCompound.concept.domainId":"Drug","objectCompound.concept.vocabularyId":"RxNorm","objectCompound.concept.conceptClassId":"Ingredient","objectCompound.concept.standardConcept":"S","objectCompound.concept.conceptCode":"6960","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":1,"objectMetaboliteCompound.name":"1'-hydroxymidazolam","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"QHSMEGADRFZVNE-UHFFFAOYSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":30,"enzymes.name":"CYP3A","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":30,"enzymes.experiment_enzyme_xref.experimentId":696,"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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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three individual experiments.[<em>K<sub>I</sub>and k<sub>inact</sub></em>(Mean ± SEM) values were determined using nonlinear least-squares regression.]</span></div>","internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":94,"cytochromeB5Id":null,"studyId":143,"experimentTypeId":1,"testSystemId":8,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme 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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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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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. The robust <em>K<sub>i</sub></em>(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.</span></li>\r\n<li><span lang=\"EN-US\">Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (<em>k<sub>inact</sub>/K<sub>I</sub></em>) was similar to that of the clinically relevant time dependent inhibitor verapamil. 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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