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Effects of oral kaempferol on the pharmacokinetics of tamoxifen and one of its metabolites, 4‐hydroxytamoxifen, after oral administration of tamoxifen to rats
Author(s) -
Piao Yongji,
Shin SangChul,
Choi JunShik
Publication year - 2008
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.593
Subject(s) - kaempferol , pharmacokinetics , cyp3a , pharmacology , tamoxifen , bioavailability , chemistry , oral administration , metabolite , active metabolite , antiestrogen , drug interaction , cyp3a4 , quercetin , endocrinology , breast cancer , medicine , cytochrome p450 , metabolism , biochemistry , cancer , antioxidant
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 © 2008 John Wiley & Sons, Ltd.