Effects of oral kaempferol on the pharmacokinetics of tamoxifen and one of its metabolites, 4-hydroxytamoxifen, after oral administration of tamoxifen to rats

It has been reported that tamoxifen is a substrate of P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A, and kaempferol is an inhibitor of P-gp and CYP3A. Hence, it could be expected that kaempferol would affect the pharmacokinetics of tamoxifen. Thus, tamoxifen was administered orally (10 mg/kg) without or with oral kaempferol (2.5 and 10 mg/kg). In the presence of kaempferol, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of tamoxifen was significantly greater, C-max was significantly higher and F was considerably greater than those without kaempferol. The enhanced bioavailability of oral tamoxifen by oral kaempferol could have been due to an inhibition of CYP3A and P-gp by kaempferol. The presence of kaempferol did not alter the pharmacokinetic parameters of a metabolite of tamoxifen, 4-hydroxytamoxifen. This could have been because the contribution of CYP3A to the formation of 4-hydroxytamoxifen is not considerable in rats. Copyright (C) 2008 John Wiley & Sons, Ltd.