EXCRETION BALANCE AND URINARY METABOLITES OF THE S-ENANTIOMER OF INDOBUFEN IN RATS AND MICE

The excretion balance and urinary metabolites of the S-enantiomer of i ndobufen, ((S)2-[p-(1-oxo-2-isoindolinyl)-phenyl]butyric acid), a plat elet aggregation inhibitor, were studied in rats and mice after oral a dministration. The urinary metabolic profile exhibited a marked specie s difference. The major metabolic pathway in the mouse was acyl glucur onidation followed by renal excretion, whereas in rat urine 5-hydroxyl ation and subsequent sulphation at the introduced hydroxyl group accou nted for almost all recovered radioactivity. Indobufen glucuronide was the major biliary metabolite in the rat, while very little indobufen glucuronide was present in the urine of intact or bile duct-cannulated rats. A marked dose-effect on the elimination and metabolism of S-ind obufen was demonstrated in the rat. The recovery (% dose) of 5-hydroxy indobufen and its sulphate after the lower dose of the enantiomer (10 mg/kg) was some 2.8-fold higher compared with the higher dose of 20 mg /kg.