| Title | Comparative bioavailability of two formulations of sibutramine. | | Author(s) | Franco Spínola AC, Almeida S, Filipe A, Neves R, Abolfathi Z, Yritia M, Anctil D, 1Medical Department, Grupo Tecnimede, Abrunheira, Sintra, Portugal, 2Department of Pharmacology and Therapeutics, Universidad Autònoma de Barcelona, Spain, 3Anapharm, Québec, Canada, and 4Anapharm Europe S.L., Barcelona, Spain | | Source | Int J Clin Pharmacol Ther 2009 Oct; 47(10):627-37. | | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19825326 |
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