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Lack of Enzyme-Inducing Effect of Rifampicin on the Pharmacokinetics of Enfuvirtide

From the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), the Thai Red Cross AIDS Research Centre, Pathumwan, Bangkok, Thailand (Dr. Boyd, Dr. Ruxrungtham); National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia (Dr. Boyd); Roche, Nutley, New Jersey (Dr. Zhang, Dr. Kolis, Dr. Nieforth, Dr. Kinchelow, Dr. Patel); XIQ Coordination, Inc., Fort Myers, Florida (Dr. Dorr); Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (Dr. Ruxrungtham); and Roche, Basel, Switzerland (Dr. Buss).

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 HIV-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 C_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.

Key Words: Enfuvirtide • pharmacokinetics • interaction • rifampicin • T-20

Address for reprints: Dr. Mark Boyd, BMBS, HIV-NAT, 104 Ratchadumri Road, Pathumwan, Bangkok 10330, Thailand.

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