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

J Clin Pharmacol. 2003 Dec;43(12):1382-91. doi: 10.1177/0091270003259220.


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 (AUC12h, Cmax, Ctrough) 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 AUC12h, Cmax, and Ctrough 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 t1/2 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Drug Interactions
  • Enfuvirtide
  • Enzyme Inhibitors / pharmacology*
  • Female
  • HIV Envelope Protein gp41 / blood
  • HIV Envelope Protein gp41 / therapeutic use
  • HIV Fusion Inhibitors / blood
  • HIV Fusion Inhibitors / pharmacokinetics*
  • HIV Fusion Inhibitors / therapeutic use
  • HIV Infections / drug therapy
  • HIV Infections / metabolism*
  • HIV-1*
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptide Fragments / pharmacokinetics*
  • Peptide Fragments / therapeutic use
  • Rifampin / pharmacology*


  • Enzyme Inhibitors
  • HIV Envelope Protein gp41
  • HIV Fusion Inhibitors
  • Peptide Fragments
  • Enfuvirtide
  • Rifampin