Species Differences in Metabolism of Sodium 2-[4-(2-Oxocyclopentylmethyl)-phenyl]propionate Dihydrate (Loxoprofen Sodium), a New Anti-Inflammatory Agent
1983
Urinary metabolites of loxoprofen-14C sodium were determined in rats, mice, dogs and monkeys after oral administration of the drug. In all these animal species, the cyclopentanone moiety of loxoprofen was predominantly reduced to trans-OH (an active principle), together with cis-OH (minor product). The monohydroxy metabolites were further hydroxylated in rats to the diols (M-4, M-5 and M-6), which were excreted in urine as the main metabolites. Mice excreted the monohydroxy metabolites mainly as their free forms. In dogs, the monohydroxy metabolites were conjugated with taurine and glucuronic acid, and monkeys furnished the ester glucuronides of the monohydroxy metabolites. Thus, species differences were observed both in the hydroxylation and in the conjugation reactions of the monohydroxy metabolites produced by the reduction of loxoprofen.
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