Effects of different meal compositions and fasted state on the oral bioavailability of etravirine

Pharmacotherapy. 2008 Oct;28(10):1215-22. doi: 10.1592/phco.28.10.1215.


Study objective: To determine the effects of various meal compositions and the fasted state on the pharmacokinetics of etravirine, a nonnucleoside reverse transcriptase inhibitor.

Design: Phase I, open-label, randomized, repeated single-dose, three-period crossover trial.

Setting: Clinical pharmacology unit.

Participants: Two parallel panels of 12 human immunodeficiency virus (HIV)-negative, healthy, male volunteers. Twenty volunteers completed the study; three withdrew consent, and one was lost to follow-up. Intervention. Panel 1 received a single dose of etravirine 100 mg after a standard breakfast, in the fasted state, and after a light breakfast (croissant). Panel 2 received the same treatment after a standard breakfast, after an enhanced-fiber breakfast, and after a high-fat breakfast. Each treatment was separated by a washout period of at least 14 days.

Measurements and main results: For each treatment, full pharmacokinetic profiles of etravirine were determined up to 96 hours after dosing. Pharmacokinetic parameters were determined by noncompartmental methods and analyzed using a linear mixed-effects model for a crossover design. The least-squares mean ratio for the area under the plasma concentration-time curve from time of administration to the last time point with a measurable concentration after dosing (AUClast) was 0.49 (90% confidence interval [CI] 0.39-0.61) for the fasted state compared with dosing after a standard breakfast. When dosing occurred after a light or enhanced-fiber breakfast, the corresponding values were 0.80 (90% CI 0.69-0.94) and 0.75 (90% CI 0.63-0.90), respectively. When administered after a high-fat breakfast the least-squares mean ratio of AUC(last) was 1.09 (0.84-1.41), compared with dosing after a standard breakfast. Adverse events were also assessed. Under all conditions, single doses of etravirine 100 mg were generally safe and well tolerated.

Conclusion: Administration of etravirine in a fasted state resulted in 51% lower mean exposure compared with dosing after a standard breakfast. Etravirine should be administered following a meal to improve bioavailability; however, differences in exposure after a standard breakfast versus a high-fat, enhanced-fiber, or light breakfast (croissant) were not considered clinically relevant.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics*
  • Biological Availability
  • Cross-Over Studies
  • Fasting*
  • Food*
  • Food-Drug Interactions*
  • Humans
  • Male
  • Middle Aged
  • Nitriles
  • Pyridazines / administration & dosage
  • Pyridazines / pharmacokinetics*
  • Pyrimidines
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / pharmacokinetics*
  • Young Adult


  • Anti-HIV Agents
  • Nitriles
  • Pyridazines
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • etravirine