Metabolism of Femoxetine

Publisher Website
Google Scholar
Abstract
Femoxetine (FG4963) an inhibitor of serotonin uptake has antidepressant activity. The metabolism of femoxetine, a serotonin uptake inhibitor, was investigated in rats, dogs, monkeys and human subjects using 2 14C-femoxetine compounds with labeling in different positions. The metabolic pathways were oxidation (and glucuronidation) and demethylation, both reactions most probably taking place in the liver. Nearly all femoxetine was metabolized, and the same metabolites were found in urine from all 4 spp. Only a small percentage of the radioactivity excreted in the urine was not identified. Rat and dog excreted more N-oxide than monkey and man, while most of the radioactivity (60-100%) in the 2 species was excreted as 2 hydroxy metabolites. The metabolic pattern in monkey and man was very similar. About 50% was excreted in the 2 spp. as 1 metabolite, formed by demethylation of a methoxy group. A demethylation of a N-CH3 group formed an active metabolite, norfemoxetine. The excretion of this metabolite in urine from man varied from 0-18% of the dose between individuals. Most of the radioactivity was excreted with the feces in rat and dog, while monkey and man excreted most of the radioactivity in urine. This difference in excretion route might be explained by the difference in metabolic pattern. No dose dependency was observed in any of the 3 animal species investigated.