Tamoxifen and toremifene concentrations in plasma are greatly decreased byrifampin

Background Rifampin (INN, rifampicin) is a potent inducer of cytochrome P45 0 (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-contro lled crossover studies. Ten (study I) or 9 (study II) healthy male voluntee rs 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 orall y. Blood samples were collected up to 336 hours after drug administration. Results: Rifampin reduced the area under the plasma concentration-time curv e (AUC) of tamoxifen by 86% (P < .001), peak plasma concentration (C-max) b y 55% (P < .001), and elimination half-life (t(1/2)) by 44% (P < .001). The AUC of toremifene was reduced by 87% (P < .001), C-max by 55% (P < .001), and t 1/2 by 44%, (P < .01) with rifampin. During the rifampin phase, the A UC of N-demethyltamoxifen was 38% (P < .001) and the AUC of N-demethyltorem ifene was 20% (P <.01) of that during the placebo phase. Conclusions: Rifampin markedly reduces the plasma concentrations of tamoxif en and toremifene by inducing their CYP3A4-mediated metabolism. Concomitant use of rifampin or other potent: inducers of CYP3A4 with tamoxifen and tor emifene may reduce the efficacy of these antiestrogens.