Abstract

Urinary excretion of nicotinamide and its metabolites in mouse, guinea pig, and hamster with a pharmacological amount of nicotinamide or N1-methylnicotinamide (MNA) was investigated to compare them with those of rat. In mouse, nicotinamide N-oxide was the most abundant metabolite, accounting for 35% of urinary excretion of nicotinamide and its metabolites, and followed by N1-methyl-2-pyridone-5-carboxamide (2-Pyr), 20%; nicotinamide, 18; MNA, 16%; and N1-methyl-4-pyridone-3-carboxamide (4-Pyr), 11%. In guinea pig, 2-Pyr was the most abundant metabolite, accounting for 80% of urinary excretion, and was followed by MNA, 11%; nicotinamide, 3%; 4-Pyr, 3%; and nicotinamide N-oxide, 3%. In hamster, nicotinamide was the most abundant metabolite, accounting for 44%, and followed by 2-Pyr, 21%; nicotinamide N-oxide, 15%; MNA, 10%; and 4-Pyr, 10%. Urinary excretion of nicotinic acid and nicotinuric acid was not detected in mouse, guinea pig, and hamster. When a pharmacological amount of nicotinamide was intraperitoneally injected into mouse, the excretion of nicotinamide N-oxide increased to 79.7% of the nicotinamide metabolites, while those of MNA (4.9%), 2-Pyr (11.2%), and 4-Pyr (6.3%) decreased. Nicotinic acid and nicotinuric acid were again not detected. When a pharmacological amount of nicotinamide was intraperitoneally injected into guinea pig and hamster, the deamidated metabolites nicotinic acid and nicotinuric acid occupied significant percentages of the nicotinamide metabolites: 50.4% and 26.3%, respectively, in guinea pig; and 7.7% and 79.5%, respectively, in hamster. The ratio of 2-Pyr to 4-Pyr excretion did not change when nicotinamide or MNA was located into mouse, guinea pig, and hamster. From these results, the catabolism of nicotinamide in rodent is discussed.

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