Studies on the Fate of Naproxen. II. Metabolic Fate in Various Animals and Man

抄録

The species differences in the metabolism of naproxen [(+)-6-methoxy-α-methyl-2-naphthaleneacetic acid] were investigated in 6 species of animals and man. ³H-naproxen was orally administered to mice, rats, rabbits, guinea pigs, dogs and miniature pigs (OHMINI-875) and cold naproxen to human subjects, and their urinary and biliary (rats only) metabolites were separated and characterized by thin-layer chromatography, gas chromatography, high-performance liquid chromatography and gas chromatographymass spectrometry. The excretion rates as % of dose of naproxen and its metabolites in the 24 hr urine were, in a decreasing order, miniature pig 82.5, mouse 80.4, rat 74.7, rabbit 70.3, guinea pig 48.5 and dog 23.0%. Naproxen and its metabolites, i.e., 6-hydroxy-α-methyl-2-naphthaleneacetic acid (6-DMN), naproxen glucuronide, 6-DMN glucuronide and 6-DMN sulfate, were found in the urines of all species. Urinary naproxen in the rat was only 0.2% and those in the other species of animals were 4.8-13.7% of the urinary radioactivity, while in man it was 1.3% of dose. The main urinary metabolite in rat, guinea pig, dog, mouse and rabbit was 6-DMN sulfate (87.3, 46.7, 42.9, 39.9 and 36.2% of the urinary radioactivity, respectively), while those in man and miniature pig were naproxen glucuronide (25.3% of dose) and 6-DMN (78.6% of the urinary radioactivity), respectively. The animals whose urinary metabolic profiles were the nearest to that of man were the guinea pig and mouse, while the animals that differed most from man in this regard were the rat and miniature pig.