Phase I study of cilostazol. Safety evaluation at increasing single doses in healthy volunteers

The safety and blood concentrations of the novel synthetic platelet aggregation inhibitor cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-qui nolinone, OPC-13013) were determined in eight healthy volunteers. The drug was orally administered to the subjects once at successive dose increments of 25, 50, 75, 100, 150, 200 and 300 mg/body. Subjective complaints were headache at 75 mg/body in 1 of 4 subjects and dull headache at 75 mg/body in 2 of 4. Each of these symptoms was also seen at higher doses in 1 to 2 of 4 subjects. Clinical laboratory values, blood pressure and heart rate were normal. Blood concentrations of the drug peaked after 3 to 4 h, the levels declining with half-lives of 2.6 to 3.2 h in the alpha-phase and 19.5 to 25.5 h in the beta-phase. The decline was generally prompt. The average peak concentrations were 283.7, 663.4, 540, 823.6, 1110.4, 1129.2 and 1623.9 mg/ml at the above doses, respectively. The effect of food on the blood concentration was also studied; however, the areas under the curve did not indicate significant differences between the fed and fasted subjects.