Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers

J Clin Pharmacol. 2006 Mar;46(3):291-300. doi: 10.1177/0091270005283467.

Abstract

Aprepitant is the first NK1 receptor antagonist approved for use with corticosteroids and 5HT3 receptor antagonists to prevent chemotherapy-induced nausea and vomiting (CINV). The effective dose to prevent CINV is a 125-mg capsule on day 1 followed by an 80-mg capsule on days 2 and 3. Study 1 evaluated the bioavailability of the capsules and estimated the effect of food. The mean (95% confidence interval [CI]) bioavailabilities of 125-mg and 80-mg final market composition (FMC) capsules, as assessed by simultaneous administration of stable isotope-labeled intravenous (i.v.) aprepitant (2 mg) and FMC capsules, were 0.59 (0.53, 0.65) and 0.67 (0.62, 0.73), respectively. The geometric mean (90% CI) area under the plasma concentration time curve (AUC) ratios (fed/fasted) were 1.2 (1.10, 1.30) and 1.09 (1.00, 1.18) for the 125-mg and 80-mg capsule, respectively, demonstrating that aprepitant can be administered independently of food. Study 2 defined the pharmacokinetics of aprepitant administered following the 3-day regimen recommended to prevent CINV (125 mg/80 mg/80 mg). Consistent daily plasma exposures of aprepitant were obtained following this regimen, which was generally well tolerated.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antiemetics / administration & dosage
  • Antiemetics / blood
  • Antiemetics / pharmacokinetics*
  • Aprepitant
  • Area Under Curve
  • Biological Availability
  • Capsules
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Monitoring
  • Female
  • Food-Drug Interactions
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Morpholines / administration & dosage
  • Morpholines / blood
  • Morpholines / pharmacokinetics*
  • Neurokinin-1 Receptor Antagonists*

Substances

  • Antiemetics
  • Capsules
  • Morpholines
  • Neurokinin-1 Receptor Antagonists
  • Aprepitant