Enantioselective pharmacokinetics of sibutramine in rat.

Racemic sibutramine is widely used to treat obesity owing to its inhibition of serotonin and noradrenaline reuptake in synapses. Although the enantioselective effects of sibutramine and its two active desmethyl-metabolites, monodesmethylsibutramine (MDS) and didesmethylsibutramine (DDS), on anorexia and energy expenditure have been elucidated, the enantioselective pharmacokinetics of sibutramine are still unclear. Therefore, we aimed to characterize the enantioselective pharmacokinetics of sibutramine and its metabolites in plasma and urine following an intravenous and a single oral administration of sibutramine in rats.

Enhanced solubility and bioavailability of sibutramine base by solid dispersion system with aqueous medium.

To develop a novel sibutramine base-loaded solid dispersion with improved solubility bioavailability, various solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction.

Enantioselective determination of sibutramine and its active metabolites in human plasma.

Although racemic sibutramine has been widely used for the treatment of obesity, its enantioselective detection method has not been elucidated in human plasma. In this report we introduce a validated analytical method for the determination of sibutramine and its two active metabolites, desmethylsibutramines using LC-MS/MS. R- and S-isomers of those compounds in human plasma were extracted using diethyl ether-hexane (4:1, v/v) followed by an addition of NaOH solution.

Analysis of enantiomers of sibutramine and its metabolites in rat plasma by liquid chromatography-mass spectrometry using a chiral stationary-phase column.

Sibutramine, a monoamine reuptake inhibitor, is used as a racemate, for the treatment of obesity. It is converted in vivo mainly to two desmethyl active metabolites, mono-desmethylsibutramine (MDS) and di-desmethylsibutramine (DDS). In the present study, we introduced a rapid and simple chromatographic method for separating the R(+)- and S(-)-isomers of sibutramine, MDS, and DDS, respectively.