Lack of enzyme-inducing effect of rifampicin on the pharmacokinetics of enfuvirtide

The primary objective was to determine whether rifampicin influences the pharmacokinetics of enfuvirtide in HIV-1-infected patients. In a single-center, open-label, one-sequence crossover, clinical pharmacology study, 12 HTV-1-infected adults received enfuvirtide (90 mg, twice daily) on days 1 to 3 and days 11 to 13 (morning dose only on days 3 and 13) and rifampicin (600 mg, once daily) from days 4 to 13. Plasma concentrations were measured for enfuvirtide and its metabolite (days 3 and 13) and rifampicin (day 13 only). The ratios of least squares means (LSM) and 90% confidence intervals for enfuvirtide and enfuvirtide metabolite pharmacokinetic parameters (AUC(12h), C-max, C-trough) were estimated in the presence and absence of rifampicin. Treatments were compared using an analysis of variance for natural log-transformed variables, with factors patient and treatment. Efficacy and safety were also monitored. Steady-state rifampicin had no appreciable effect on any of the pharmacokinetic parameters assessed for either enfuvirtide or its metabolite. The ratio of LSM for AUC(12h), C-max, and G(trough) for enfuvirtide was 97.5%, 103%, and 84.9%, respectively, and 108%, 112%, and 92.9%, for the enfuvirtide metabolite. Rifampicin did not affect the t(1/2) of enfuvirtide or its metabolite. There were no unexpected effects of rifampicin on the short-term antiviral effect or safety of the administered antiretroviral treatment. The pharmacokinetics of enfuvirtide are not induced by a 10-day pretreatment with rifampicin.