Metabolism and excretion of [14C]taranabant, a cannabinoid-1 inverse agonist, in humans

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 (∼ 92%), with the majority of the dose (∼ 87%) excreted into faeces and a much smaller fraction (∼ 5%) into urine.Taranabant was absorbed rapidly, with Cmax 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 ∼ 12–24% and 33–42%, respectively, of the plasma radioactivity for up to 48 h. A second monohydroxylated metabolite, designated as M1a, represented ∼ 10–12% of th...