PURPOSE: The purpose of this study was to characterize the food effect on the pharmacokinetics of sibutramine and its pharmacologically active metabolites. METHODS: This was an open label, single dose, crossover study completed by six healthy males. A single dose of sibutramine 15 mg was administered orally under fasting and fed conditions. Plasma concentrations of sibutramine and its metabolites were determined by LC/MS/MS: Non-compartmental pharmacokinetics and statistical analysis were performed using SAS. RESULTS: The food intake increased significantly AUCs and C(max) of sibutramine and its M1 metabolite, but did not affect M2 metabolite. When sibutramine was administered with food, the T(max) was delayed by 2 to 4 hours for sibutramine, M1 and M2 metabolites as stated in the literature. CONCLUSIONS: The results of this study indicate that sibutramine is measurable using a sensitive bioanalytical method. In contrast with what is reported in the product monograph, this study demonstrated that the bioavailability of sibutramine and M1 metabolite was significantly increased with administration with food. The results confirmed lack of food effect on the pharmacokinetics of M2 metabolite. These relatively large food effect observed for sibutramine and M1 metabolite, could have implication for the efficacy and safety of the drug.
RCT Entities:
PURPOSE: The purpose of this study was to characterize the food effect on the pharmacokinetics of sibutramine and its pharmacologically active metabolites. METHODS: This was an open label, single dose, crossover study completed by six healthy males. A single dose of sibutramine 15 mg was administered orally under fasting and fed conditions. Plasma concentrations of sibutramine and its metabolites were determined by LC/MS/MS: Non-compartmental pharmacokinetics and statistical analysis were performed using SAS. RESULTS: The food intake increased significantly AUCs and C(max) of sibutramine and its M1 metabolite, but did not affect M2 metabolite. When sibutramine was administered with food, the T(max) was delayed by 2 to 4 hours for sibutramine, M1 and M2 metabolites as stated in the literature. CONCLUSIONS: The results of this study indicate that sibutramine is measurable using a sensitive bioanalytical method. In contrast with what is reported in the product monograph, this study demonstrated that the bioavailability of sibutramine and M1 metabolite was significantly increased with administration with food. The results confirmed lack of food effect on the pharmacokinetics of M2 metabolite. These relatively large food effect observed for sibutramine and M1 metabolite, could have implication for the efficacy and safety of the drug.