Metabolism of femoxetine, its enantiomer and the racemate in rat liver microsomes.
The substrates were incubated at various concentrations for 30 minutes with rat liver microsomes. FG 4962 was metabolized more rapidly than femoxetine, i.e. approximately 20% more FG 4962 was degraded during 30 min incubation at saturating substrate concentration. Femoxetine was metabolized predominantly by O- and N-demethylation, almost equally, whereas FG 4962 was metabolized mainly by N-demethylation. Chiralphase HPLC studies revealed that incubation of the racemate with rat liver microsomes resulted in the impairment of the N-demethylating metabolic route for femoxetine, while the metabolism of FG 4962 was not impaired. Induction of the rat livers with sodium phenobarbital gave almost the same qualitative results but with increased rates of metabolism.
Nordholm
L
L
Dalgaard
L
L
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D010880:Piperidines; C010655:femoxetine