Eigo Takabatake

Further Studies on the Metabolism of Mepirizole: The Isolation of a New Metabolite from Dog Urine and Species Differences in Urinary Metabolites

1. A new metabolite of mepirizole was isolated from dog urine and characterized as 1-(4-methoxy-6-hydroxymethyl-2-pyrimidinyl)-3-hydroxymethyl-5-methoxypyrazole (UNM–6) from mass and n.m.r. spectra.2. Urinary excretion patterns of mepirizole metabolites in man, rat, rabbit, guinea pig, dog, and cat were compared. The major metabolite was 1-(4-methoxy-6-methyl-2-pyrimidinyl)-5-methoxypyrazole-3-carboxylic acid (UAM–1) in man, rabbit, guinea pig, and dog, and 1-(4-methoxy-6-methyl-2-pyrimidinyl)-3-methyl-4-hydroxy-5-methoxypyrazole sulphate (URM–1) in rat and cat.3. The in vitro experiments using rabbit liver preparation showed that microsomes oxidized mepirizole to 1-(4-methoxy-6-methyl-2-pyrimidinyl)-3-hydroxymethyl-5-methoxypyrazole (UNM–2) and soluble fraction converted UNM–2 to UAM–1. The production of other metabolites was not detected under the in vitro conditions examined.