The absorption, distribution and excretion of a new antithrombotic and vasodilating agent, cilostazol, in rat, rabbit, dog and man

Abstract

The absorption, distribution and excretion of a new antithrombotic and vasodilating agent, 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, rabbits, dogs and man. After the oral administration of 14C-cilostazol at a dose of 10 mg/kg in male and female rats and rabbits, and at a dose of 3 mg/kg in dogs, the Tmax, Cmax and T1/2 of the radioactivity were 2 h, 710.5 ng eq X ml-1 and 2.5 h in male rats, 4 h, 11 002.8 ng eq X ml-1 and 3.7 h in female rats, 8 h, 358.1 ng eq X ml-1 and 6.9 h in rabbits, and 3 h, 559.4 ng eq X ml-1 and 1.6 h in dogs, respectively. After the oral administration of 14C-cilostazol at a dose of 10 mg/kg in rats, tissue concentrations of radioactivity in female rats were about 3 to 5 times as high as those in male rats. The blood and tissue concentrations of radioactivity in male and female rats showed a marked sex difference. However, the concentrations in the blood in both male and female rats declined rapidly. There was no evidence of the accumulation of radioactivity in the tissues due to repeated oral administrations of 14C-cilostazol at a dose of 3 mg/kg once a day for 21 days in male rats.(ABSTRACT TRUNCATED AT 250 WORDS)