The metabolism of a new antithrombotic and vasodilating agent, cilostazol, in rat, dog and man.

The metabolism of cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)- qui nolinone, OPC-13013) was studied after the oral administration of cilostazol or 14C-cilostazol in rats, dogs and man. Metabolites of cilostazol identified in the rat, dog and human plasma and urine were monohydroxycilostazol (OPC-13213, OPC-13217, OPC-13366, OPC-13371, OPC-13215 and OPC-13326), monohydroxydehydrocilostazol (OPC-13269 and OPC-13388), 3,4-dihydro-6-hydroxy-2(1H)-quinolinone (6-HQ), their conjugates and dehydrocilostazol (OPC-13015). Major metabolites detected in the rat plasma were OPC-13015, OPC-13217 and OPC-13213, and the plasma concentration of OPC-13015 was 53 to 79% of that of cilostazol. In the dog plasma, major metabolites detected were OPC-13213, OPC-13366 and OPC-13015, and the AUC of OPC-13213 was 79.7% of that of cilostazol. In the human plasma, major metabolites detected were OPC-13015 and OPC-13213, and their AUC were 11.7 and 9.1% of that of cilostazol, respectively. Monohydroxycilostazol and monohydroxydehydrocilostazol were detected at 8.5% of dose in the rat urine and 8.7% in the dog urine, and OPC-13213 showed the highest concentration of these. The conjugates of these and 6-HQ were detected at 0.4 and 24.5%, respectively, in the rat urine and 2.4 and 3.7%, respectively, in the dog urine. These conjugates were mainly sulfate in rats and glucuronide in dogs. In the human urine, OPC-13213 showed the highest concentration, and the conjugates were mainly glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS)