Species differences in the metabolic C- and N-oxidation, and N-methylation of [¹⁴C]pyridine in vivo

L. A. Damani Drug Metabolism and Toxicology Group, Department of Pharmacy, University of Manchester, Manchester, M13 9PL, UK

P. A. Crooks Drug Metabolism and Toxicology Group, Department of Pharmacy, University of Manchester, Manchester, M13 9PL, UK; College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40506, USA

M. S. Shaker Drug Metabolism and Toxicology Group, Department of Pharmacy, University of Manchester, Manchester, M13 9PL, UK

J. Caldwell Department of Biochemical and Experimental Pharmacology, St Mary's Hospital Medical School, Paddington, London, W2 1PG, UK

J. D'souza Department of Biochemical and Experimental Pharmacology, St Mary's Hospital Medical School, Paddington, London, W2 1PG, UK

R. L. Smith Department of Biochemical and Experimental Pharmacology, St Mary's Hospital Medical School, Paddington, London, W2 1PG, UK

Abstract

1. The metabolism of [2,6-¹⁴C]pyridine in vivo has been investigated in the rat, hamster, mouse, gerbil, rabbit, guinea-pig, cat and man, and the quantitative determination of the various urinary metabolites carried out by radiochromatographic analysis.

2. Unchanged pyridine and its N-methylated metabolite, N-methylpyridinium ion, were determined using a Partisil-10 SCX cation-exchange h.p.l.c. column, whereas the C- and N-oxidation products were assayed by reverse-phase chromatography, using a Partisil-10 ODS column.

3. Most of the species studied produce pyridine N-oxide, N-methylpyridinium ion, 2-pyridone, 3-hydroxypyridine and 4-pyridone as metabolites, but the proportion of the dose excreted as each of these metabolites is species-dependent.

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Species differences in the metabolic C- and N-oxidation, and N-methylation of [¹⁴C]pyridine in vivo

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Species differences in the metabolic C- and N-oxidation, and N-methylation of [14C]pyridine in vivo

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Species differences in the metabolic C- and N-oxidation, and N-methylation of [¹⁴C]pyridine in vivo