Metabolic fate of loxistatin in rat

1. The urinary and plasma metabolites of 14C-loxistatin, a new thiol protease inhibitor, were studied after oral administration to rats. 2. The major metabolites in urine were identified as loxistatin acid (M-1), a pharmacologically active form, and its hydroxy metabolites (M-4a and M-4b). These metabolites were also shown to be the major metabolites in plasma. 3. The inhibitory activity of the synthetic metabolite, M-4b, on papain was almost the same as that of loxistatin acid.