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\r\n- The 7-fold shift observed with mitragynine against intestinal and hepatic CYP3A activity suggests mitragynine is a time dependent inhibitor. IC50values were within the concentration range reported in post-mortem human plasma and tissues. Although no leftward shift was observed for CYP2D6, the IC50was also within the concentration range reported in post-mortem human plasma and tissues.
\r\n- Mitragynine was shown to be a strong competitive inhibitor of CYP2D6 activity. The robust Ki(~1 µM) will be applied to mechanistic and PBPK models to predict drug interaction potential.
\r\n- Mitragynine is a time dependent inhibitor of both intestinal and hepatic CYP3A activity. The efficiency of inactivation (kinact/KI) was similar to that of the clinically relevant time dependent inhibitor verapamil. The kinetic parameters, KIand kinactwill be applied to mechanistic and PBPK models to predict drug interaction potential.
\r\n
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