Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects

J Clin Pharmacol. 2007 Jul;47(7):834-40. doi: 10.1177/0091270007301800. Epub 2007 May 24.

Abstract

Fosaprepitant is an intravenous formulation of aprepitant, an oral NK1 antagonist used to prevent chemotherapy-induced nausea and vomiting. This randomized study was designed to evaluate fosaprepitant in polysorbate 80 vehicle for tolerability and bioequivalency to aprepitant. Tolerability was assessed by physical and laboratory examinations and adverse events. Plasma collected for 72 hours was assayed for aprepitant and fosaprepitant. Analysis of variance models were applied to natural log-transformed aprepitant area under the curve (AUC) data. Fosaprepitant up to 150 mg (1 mg/mL) was generally well tolerated. Fosaprepitant 115 mg was AUC bioequivalent to aprepitant 125 mg; the 90% confidence interval for the geometric mean ratio of aprepitant AUC for fosaprepitant 115 mg/aprepitant 125 mg fell within prespecified equivalence bounds of 0.80 to 1.25.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Analysis of Variance
  • Antiemetics / administration & dosage
  • Antiemetics / adverse effects*
  • Antiemetics / blood
  • Antiemetics / pharmacokinetics
  • Aprepitant
  • Area Under Curve
  • Cross-Over Studies
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Morpholines / administration & dosage
  • Morpholines / adverse effects*
  • Morpholines / blood
  • Morpholines / pharmacokinetics
  • Neurokinin-1 Receptor Antagonists*
  • Prodrugs / administration & dosage
  • Prodrugs / adverse effects*
  • Prodrugs / pharmacokinetics
  • Therapeutic Equivalency

Substances

  • Antiemetics
  • L 758298
  • Morpholines
  • Neurokinin-1 Receptor Antagonists
  • Prodrugs
  • Aprepitant
  • fosaprepitant