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• W2314342110 abstract "We studied the factors related to species and sex difference contributing to metabolic patterns of[3, 4-di(4-methoxyphenyl)-5-isoxazolyl] acetic acid (mofezolac) in vitro, and the metabolic pathway determined after administrations of metabolites of mofezolac. Also the metabolism of mofezolac in germ free rats, and the in situ absorption rates using recirculation perfusion of mofezolac and the metabolites were studied.1. Mofezolac demethylase activities in monkeys and rats were highest among investigated animals, following by the activity in mice. The activity in the dog was about 10 times lower than that in mice. Sex difference in mofezolac demethylase activity was not observed in the rats. UDP-glucuronatemofezolac glucuronosyltransferase activities in the monkey and the dog were high, and that in the rat was about 1/3 lower than that in the monkey and the dog.2. Mofezolac sulfotransferase activity in rats cytosol was much higher than the activities in other investigated animals. Sex deference was observed in rats ; the activity in male rats was about 3 times higher than that in female rats. Therefore, the total amount of sulfoconjugate of[3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)-5-isoxazolyl] acetic acid(3-DM-mofezolac) in vivo reflects the sulfotransferase activity of liver.3. After administrations of mofezolac metabolites, the main metabolite in bile derived from 3-DM-mofezolac was 4-[4-(4-methoxyphenyl)-5-carboxymethyl-3-isoxazolyl] phenyl hydrogeo sulfate (3-DM-mofezolac-sulfate), and the main metabolite derived from[4-(4-hydroxyphenyl)-3-(4-methoxyphenyl)-5-isoxazolyl]acetic acid (4-DM-mofezolac) was[3, 4-di(hydroxyphenyl)-5-isoxazolyl] acetic acid (3, 4-DM -mofezolac-sulfate). These results explain that 3-(4-methoxyphenyl) was desmethylated easier than 4-(4-methoxyphenyl). No sulfoconjugate of 4-DM-mofezolac was formed after administration of 4-DM-mofezolac. This result suggested that sulfoconjugate was not formed by binding of a sulfate directly to OH in the phenyl group on the side of 4-position of isoxazol.4. The main fecal metabolite in SPF rats was 3-DM-mofezolac, while in germ free rats was 3-DM-mofezolac-sulfate. This result clarified that 3-DM-mofezolac-sulfate was degraded by intestinal microflora.5. The absorption rate constant of mofezolac from the small intestine was close to the absorption rate constants of indomethacin or salicylic acid using in situ recirculation perfusion system. In the stomach, mofezolac was absorbed in about 1/2 of that in small intestine when the perfusate was acidic (pH3). The absorption rate constant of 3-DMmofezolac-sulfate was about 8 times lower than the that of mofezolac. 3-DM-mofezolacsulfate was hardly absorbed." @default.
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• W2314342110 date "1990-01-01" @default.
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• W2314342110 title "Pharmacokinetic studies of mofezolac. III: Differences of metabolic pathways brought by animal differences." @default.
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• W2314342110 doi "https://doi.org/10.2133/dmpk.5.429" @default.
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