ABSTRACT
The metabolic fate in animals of the antidepressant compound fluvoxamine was investigated. The 14C-labeled drug was administered orally to dogs, rats, hamsters, and mice, and excretion in urine and feces was measured. Chromatographic patterns of the urines were developed by high performance liquid chromatography. These patterns were used as guides in the isolation of the metabolites, its initial step consisting of concentration of the radioactivity in the urine pools in a conical precolumn, followed by separation in the same HPLC system as used for the metabolite patterns. Altogether, 32 radioactive substances were isolated from the urine pools of the four animal species. They were all identified by the combined use of proton nuclear magnetic resonance and mass spectrometry, and by information obtained from chromatographic behavior and color reactions. Several of the 32 compounds were identical, leaving a total of 11 different metabolites in the four species. In all the animal species, the main focus of fluvoxamine degradation was its aliphatic methoxyl group. In three species, this resulted in the corresponding carboxylic acid as the main metabolite, but in the mouse the corresponding alcohol, in glucuronidated form, was at least as important. In mouse and hamster, the methyl ester was a minor metabolite. Products of acetylation or oxidative removal of the primary amino group accounted for only minor proportions of the metabolite patterns. While fluvoxamine itself has the (E)-configuration, several metabolites occurred both in the (E)- and the (Z)-form. The parent compound was isolated only from the urine of dogs, it accounted for less than 10% of the urinary radioactivity.
