Metabolism and excretion of [14C]taranabant, a cannabinoid-1 inverse agonist, in humans.
Xenobiotica
; 40(10): 691-700, 2010 Oct.
Article
in En
| MEDLINE
| ID: mdl-20722472
ABSTRACT
Taranabant (N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide or MK-0364) is an orally active inverse agonist of the cannabinoid 1 (CB-1) receptor that was under development for the management of obesity. The metabolism and excretion of taranabant were investigated following a single oral dose of 5 mg/201 µCi [14C]taranabant to six healthy male subjects. The overall excretion recovery of the administered radioactivity was nearly quantitative (â¼92%), with the majority of the dose (â¼87%) excreted into faeces and a much smaller fraction (â¼5%) into urine. Taranabant was absorbed rapidly, with C(max) of radioactivity attained at 1-2-h postdose. The parent compound and its monohydroxylated metabolite, M1, were the major radioactive components circulating in plasma and comprised â¼12-24% and 33-42%, respectively, of the plasma radioactivity for up to 48 h. A second monohydroxylated metabolite, designated as M1a, represented â¼10-12% of the radioactivity in the 2- and 8-h postdose plasma profiles. Metabolite profiles of the faeces samples consisted mainly of the (unabsorbed) parent compound and multiple diastereomeric carboxylic acid derivatives derived from oxidation of the geminal methyl group of the parent compound and of the hydroxylated metabolite/s. These data suggest that, similar to rats and monkeys, taranabant is primarily eliminated in humans via oxidative metabolism and excretion of metabolites via the biliary/faecal route.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridines
/
Receptor, Cannabinoid, CB1
/
Amides
Limits:
Humans
/
Male
Language:
En
Journal:
Xenobiotica
Year:
2010
Type:
Article
Affiliation country:
United States