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• W1534070506 abstract "Abstract Objectives It has been reported that docetaxel is a P-glycoprotein substrate and is metabolized via the cytochrome P450 (CYP) 3A subfamily in rats. Tesmilifene is a substrate of the CYP3A subfamily and is an inhibitor of P-glycoprotein. Thus, the effects of various doses of tesmilifene on the pharmacokinetics of intravenous and orally administered docetaxel have been investigated in rats. Methods Docetaxel (20 mg/kg as base) was administered intravenously and orally without and with tesmilifene (5, 10, and 20 mg/kg) in rats. Key findings After intravenous administration of docetaxel with tesmilifene, the values of nonrenal clearance (CLNR) and area under the plasma concentration–time (AUC) for docetaxel were comparable with those without tesmilifene. Tesmilifene did not increase the values of AUC or of absolute oral bioavailability (F) for docetaxel after oral administration of docetaxel with tesmilifene. Conclusions The inhibition for the metabolism of docetaxel via hepatic and intestinal CYP3A subfamily, and inhibition of P-glycoprotein-mediated efflux of docetaxel in the intestine by tesmilifene were almost negligible. The extremely low value of F for docetaxel was due to the incomplete absorption from the gastrointestinal tract and considerable first-pass metabolism of docetaxel in rats." @default.
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• W1534070506 date "2010-07-21" @default.
• W1534070506 modified "2023-09-27" @default.
• W1534070506 title "Effects of tesmilifene, a substrate of CYP3A and an inhibitor of P-glycoprotein, on the pharmacokinetics of intravenous and oral docetaxel in rats" @default.
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• W1534070506 doi "https://doi.org/10.1111/j.2042-7158.2010.01129.x" @default.
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