Comparative bioavailability of two formulations of sibutramine.

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 (AUC 0-t ) and the maximum observed concentration (C max ). 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 C max , 90.37 ― 123.18% for AUC 0-t and 91.20 ― 122.38% for AUC inf for R-sibutramine and 88.27 ― 124.08% for C max , 86.15 - 121.78% for AUC 0-t and 88.02 ― 120.96% for AUC inf 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.