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Reduced Bioavailability of Tamoxifen and its Metabolite 4‐Hydroxytamoxifen After Oral Administration with Biochanin A (an Isoflavone) in Rats
Author(s) -
Singh Sheelendra Pratap,
Raju K. S. R.,
Ali Mushir M.,
Kohli Kanchan,
Jain Girish Kumar
Publication year - 2012
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3652
Subject(s) - tamoxifen , bioavailability , biochanin a , pharmacology , pharmacokinetics , metabolite , oral administration , dose , active metabolite , chemistry , cyp3a , cyp3a4 , endocrinology , medicine , cytochrome p450 , metabolism , breast cancer , cancer , genistein , daidzein
The aim of this study was to investigate the effect of biochanin A (BCA) on the pharmacokinetics of tamoxifen, a substrate of P‐glycoprotein (P‐gp) and cytochrome 3A (CYP3A), in female rats. The tamoxifen was administered orally (10 mg/kg) without or with oral BCA (100 mg/kg) in female rats. As BCA is an inhibitor of CYP 3A and P‐gp it was expected to increase the bioavailability of tamoxifen, a known substrate of CYP3A4/Pgp. Surprisingly, compared with the control group (treated with tamoxifen alone), BCA pretreated animals showed significantly ( p < 0.05) decreased area under the plasma concentration–time curve from time zero to time infinity (AUC 0‐∞ ) and peak tamoxifen concentrations ( C max ). Consequently, the relative bioavailability (RB%) of tamoxifen co‐administered with BCA was remarkably decreased compared with the control group. The AUC 0‐∞ and C max of 4‐hydroxytamoxifen in BCA pretreated rats were also significantly ( p < 0.05) lower than those from the control group. However, there were no apparent changes in the metabolite ratio (MR; AUC 0‐∞ of 4‐hydroxytamoxifen to tamoxifen) by co‐administration of BCA. If the results of this study are further confirmed by clinical trials, tamoxifen dosages should be adjusted to avoid potential drug interaction when tamoxifen is used clinically in combination with BCA and BCA‐containing dietary supplements. Copyright © 2011 John Wiley & Sons, Ltd.