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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Noh, Keumhan Bae, Kyoungjin Min, Bokyoung Kim, Eunyoung Kwon, Kwang-il Jeong, Taecheon Kang, Wonku |
| Description | Author Affiliation: Noh K ( College of Pharmacy, Catholic University of Daegu, Kyoungbuk 712-702, Korea.) |
| Abstract | 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. The absolute bioavailability of sibutramine was only about 7%. The pharmacologically less effective S-isomer of DDS was predominant in the plasma: the C ( max ) and the AUC ( inf ) were 28 and 30 times higher than those of the R-isomer, respectively (p<0.001). In the urine, the concentrations of the R-isomers of hydroxylated DDS and hydroxylated and carbamoylglucuronized MDS and DDS appeared to be 11.3-, 5.1-, and 5.3-times the concentrations of the respective S-isomers. Thus, regardless of increased potency than the S-enantiomers, the R-enantiomers of the sibutramine metabolites MDS and DDS were present at lower concentrations, owing to their rapid biotransformation to hydroxylated and/or carbamoylglucuronized forms and their faster excretion in the urine. The present study is the first to elucidate the enantioselective pharmacokinetics of sibutramine in rats. |
| File Format | HTM / HTML |
| ISSN | 02536269 |
| Issue Number | 2 |
| Volume Number | 33 |
| e-ISSN | 19763786 |
| Journal | Archives of Pharmacal Research |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2010-02-01 |
| Publisher Place | Korea (South) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Cyclobutanes Pharmacokinetics Administration, Oral Animals Biological Availability Administration & Dosage Chemistry Injections, Intravenous Male Rats Rats, Sprague-dawley Stereoisomerism Comparative Study Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Organic Chemistry Drug Discovery Molecular Medicine |
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