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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Tamoxifen and toremifene concentrations in plasma are greatly decreased by rifampin.

BACKGROUND: Rifampin (INN, rifampicin) is a potent inducer of cytochrome P450 ( CYP) enzymes involved in drug metabolism and therefore causes many drug interactions. METHODS: The effects of rifampin on the pharmacokinetics of tamoxifen (study I) and toremifene (study II) were examined in 2 randomized, placebo-controlled crossover studies. Ten (study I) or 9 (study II) healthy male volunteers took either 600 mg rifampin or placebo orally once a day for 5 days. On the sixth day, 80 mg tamoxifen or 120 mg toremifene was administered orally. Blood samples were collected up to 336 hours after drug administration. RESULTS: Rifampin reduced the area under the plasma concentration-time curve (AUC) of tamoxifen by 86% (P < .001), peak plasma concentration (Cmax) by 55% (P < .001), and elimination half-life (t1/2) by 44% (P < .001). The AUC of toremifene was reduced by 87% (P < .001), Cmax by 55% (P < .001), and t1/2 by 44% (P < .01) with rifampin. During the rifampin phase, the AUC of N-demethyltamoxifen was 38% (P < .001) and the AUC of N-demethyltoremifene was 20% (P < .01) of that during the placebo phase. CONCLUSIONS: Rifampin markedly reduces the plasma concentrations of tamoxifen and toremifene by inducing their CYP3A4-mediated metabolism. Concomitant use of rifampin or other potent inducers of CYP3A4 with tamoxifen and toremifene may reduce the efficacy of these antiestrogens.[1]


  1. Tamoxifen and toremifene concentrations in plasma are greatly decreased by rifampin. Kivistö, K.T., Villikka, K., Nyman, L., Anttila, M., Neuvonen, P.J. Clin. Pharmacol. Ther. (1998) [Pubmed]
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