Comparative bioavailability of two formulations of sibutramine

Int J Clin Pharmacol Ther. 2009 Oct;47(10):627-37. doi: 10.5414/cpp47627.

Abstract

This study was conducted in order to compare the bioavailability of two capsule formulations containing 15 mg of sibutramine, N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine hydrochloride monohydrate, 84485-00-7 CAS registry number. 62 healthy subjects were enrolled in a single-center, randomized, single-dose, open-label, 2-way crossover study, with a minimum washout period of 14 days. Plasma samples were collected up to 72.0 hours post-dosing. R-sibutramine, S-sibutramine, N-mono-desmethyl-sibutramine (M1) and N-di-desmethyl-sibutramine (M2) levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection, LC/MS/MS method. Pharmacokinetic parameters used for bioequivalence assessment were the area under the concentration-time curve from time zero to time of last non-zero concentration (AUC0-t) and the maximum observed concentration (Cmax). These parameters were determined from sibutramine enantiomers as well from M1 and M2 concentration data using non-compartmental analysis. The 90% confidence intervals obtained by analysis of variance were 89.25 - 122.88% for Cmax, 90.37 - 123.18% for AUC0-t and 91.20 - 122.38% for AUCinf for R-sibutramine and 88.27 - 124.08% for Cmax, 86.15 - 121.78% for AUC0-t and 88.02 - 120.96% for AUCinf for S-sibutramine. These results were all within the range of 80.00 - 125.00% established by regulatory requirements. Bioequivalence between formulations was concluded both in terms of rate and extent of absorption.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Appetite Depressants / administration & dosage
  • Appetite Depressants / adverse effects
  • Appetite Depressants / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Capsules
  • Chromatography, Liquid / methods
  • Cross-Over Studies
  • Cyclobutanes / administration & dosage
  • Cyclobutanes / adverse effects
  • Cyclobutanes / pharmacokinetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Tandem Mass Spectrometry / methods
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Appetite Depressants
  • Capsules
  • Cyclobutanes
  • sibutramine