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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. 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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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