IN-VIVO BIOTRANSFORMATION OF FENOCTIMINE IN RAT, DOG AND MAN

1. The metabolism of fenoctimine (Fn) was studied in rat, dog and man following administration of C-14-Fn sulphate. 2. Seventeen Fn metaboli tes were isolated by hplc and tie from rat bile, dog bile, dog urine, human urine, human faecal extracts, and human plasma and identified us ing nmr and MS. 3. The identified metabolites accounted for 75% of tot al radioactivity in rat bile, 80% in dog bile, and 40% in dog urine sa mples. In man, 90% of the urinary, 70% of the faecal, and > 50% of the plasma total radioactivity were identified. 4. Three major pathways f or Fn metabolism were proposed. These pathways involved imino-bond cle avage, aromatic hydroxylation and oxidation of the aliphatic chain. 5. The imino-bond cleavage pathway was dominant in all species. However, the other two pathways differed in quantitative importance among the species studied. 6. The aromatic hydroxylation pathway appeared to be the most important means of biotransformation of Fn in dog since all b ut two of the metabolites were formed by this route. 7. The aliphatic oxidation pathway appeared to be important to the biotransformation of Fn in man and produced three major metabolites.