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 (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.
Franco Spínola
A C
AC
Medical Department, Grupo Tecnimede, Sintra, Portugal. dmed.ct@tecnimede.pt
Almeida
S
S
Filipe
A
A
Neves
R
R
Abolfathi
Z
Z
Yritia
M
M
Anctil
D
D
D000328:Adult; D001067:Appetite Depressants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002853:Chromatography, Liquid / Q000379:methods; D018592:Cross-Over Studies; D003503:Cyclobutanes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods; D013810:Therapeutic Equivalency; D055815:Young Adult
D001067:Appetite Depressants; D002214:Capsules; D003503:Cyclobutanes; C058254:sibutramine