Sibutramine is metabolized in the liver principally by the cytochrome P450 (3A₄) isoenzyme, to desmethyl metabolites, M₁ and M₂. These active metabolites are further metabolized by hydroxylation and conjugation to pharmacologically inactive metabolites, M₅ and M₆. Following oral administration of radiolabeled sibutramine, essentially all of the peak radiolabeled material in plasma was accounted for by unchanged sibutramine (3%), M₁ (6%), M₂ (12%), M₅ (52%), and M₆ (27%).

M₁ and M₂ plasma concentrations reached steady-state within four days of dosing and were approximately two-fold higher than following a single dose. The elimination half-lives of M₁ and M₂, 14 and 16 hours, respectively, were unchanged following repeated dosing.

Excretion

Approximately 85% (range 68-95%) of a single orally administered radiolabeled dose was excreted in urine and feces over a 15-day collection period with the majority of the dose (77%) excreted in the urine. Major metabolites in urine were M₅ and M₆; unchanged sibutramine, M₁, and M₂ were not detected. The primary route of excretion for M₁ and M₂ is hepatic metabolism and for M₅ and M₆ is renal excretion.

Summary of Pharmacokinetic Parameters

Effect of Food

Bookmark this page: