Metabolická studie sibutraminu

Abstract

Obesity represents a serious problem especially in American and European populations. Pharmacotherapy in combination with a reduced calorie diet is recommended for obese patients as a multi-modal approach to weight loss. Sibutramine hydrochloride monohydrate represents one of the few established and well-proven agents available for treatment of obesity. It is sold as a racemic mixture under the trade-name Meridia, Reductil or Lindaxa. It acts as a monoamine reuptake inhibitor. The weight loss of patients induced by sibutramine is thought to be due to a combination of serotonin- and noradrenaline-mediated mechanisms that increase both satiety and energy expenditure. In organisms, sibutramine is rapidly demethylated to form metabolites M1 and M2. These metabolites contribute largely to the pharmacological effects of sibutramine and the pharmacokinetic characteristics of M1 and M2 were thoroughly studied in human plasma. Although sibutramine is widely used for the treatment of obesity almost ten years, the published information on the further metabolic fate of metabolites M1 and M2 as well as on the elimination of sibutramine from the body is almost exclusively limited to package inserts of the product. To address this issue we determined the routes of elimination of sibutramine in humans via urine. LC-API/MS...