Grubb N, Caldwell J, Strolin-Benedetti M
Department of Pharmacology and Toxicology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, University of London, U.K.
Biochem Pharmacol. 1993 Oct 19;46(8):1507-10. doi: 10.1016/0006-2952(93)90119-h.
The excretion balance and urinary metabolites of the S-enantiomer of indobufen, ((S)2-[p-(1-oxo-2-isoindolinyl)-phenyl]butyric acid), a platelet aggregation inhibitor, were studied in rats and mice after oral administration. The urinary metabolic profile exhibited a marked species difference. The major metabolic pathway in the mouse was acyl glucuronidation followed by renal excretion, whereas in rat urine 5-hydroxylation and subsequent sulphation at the introduced hydroxyl group accounted 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-indobufen was demonstrated in the rat. The recovery (% dose) of 5-hydroxyindobufen 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.
