Abstract
Docetaxel is a P-glycoprotein (P-gp) substrate and metabolized via cytochrome P450 (CYP) 3A subfamily in rats. Morin is an inhibitor of both CYPs and P-gp. Hence, the effects of morin on the intravenous and oral pharmacokinetics of docetaxel were investigated using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor rats (DMBA rats) as an animal model of human breast cancer. Docetaxel was administered intravenously (4 mg/kg) and orally (20 mg/kg) without and with morin (15 mg/kg) in DMBA rats. After the intravenous administration of docetaxel in control and DMBA rats with and without morin, the values of non-renal clearance and area under the plasma concentration-time (AUC) for docetaxel were comparable. Morin did not increase AUC or the absolute oral bioavailability (F) for docetaxel after the oral administration of docetaxel in control and DMBA rats with and without morin. The inhibition of hepatic and intestinal metabolism of docetaxel by morin and/or DMBA and the effect of intestinal P-gp inhibition by morin on the pharmacokinetics of docetaxel did not seem to be considerable in DMBA-induced mammary tumor rats.
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