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Abstract
1. The metabolism of fenoctimine (Fn) was studied in rat, dog and man following administration of 14C-Fn sulphate.
2. Seventeen Fn metabolites were isolated by hplc and tlc from rat bile, dog bile, dog urine, human urine, human faecal extracts, and human plasma and identified using nmr and MS.
3. The identified metabolites accounted for 75% of total radioactivity in rat bile, 80% in dog bile, and 40% in dog urine samples. In man, 90% of the urinary, 70% of the faecal, and > 50% of the plasma total radioactivity were identified.
4. Three major pathways for Fn metabolism were proposed. These pathways involved imino-bond cleavage, 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 but 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.