Antiaggregatory effect of oral cilostazol and recovery of platelet aggregability in patients with cerebrovascular disease.

A new antithrombotic drug, cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)- qui nolinone, OPC-13013), was orally administered at 50, 100, 150 and 200 mg daily for four weeks to 24 patients with cerebrovascular diseases including cerebral thrombosis, cerebral embolism, transient ischemic attacks and cerebral arteriosclerosis. The drug effect on platelet aggregation induced by adenosine diphosphate (ADP), collagen, epinephrine and arachidonic acid and the recovery of platelet aggregation after drug withdrawal were monitored with time by determining the plasma concentrations of the drug. Prior to the repetitive administration study, the antiplatelet-aggregating effect of the drug was examined by single administration at 50 and 100 mg to six patients each. The dose of 50 mg was not sufficiently effective, but the dose of 100 mg significantly (p less than 0.05) reduced aggregation induced by collagen and arachidonic acid at 6 h suggesting the therapeutic value of the drug even by single administration. Following this study, the antiplatelet-aggregating effect of the drug was determined after four weeks of treatment. The pretreatment values for ADP-induced aggregation were 72.7, 72.1, 70.5 and 78.8% in the 50 mg/day (once daily), 100 mg/day (50 mg twice a day), 150 mg/day (50 mg three times a day) and 200 mg/day (100 mg twice a day) dosage groups, respectively. The aggregation rates determined after 4 weeks of treatment were 60.8, 56.8, 46.0 and 43.8%, respectively, and the values obtained at 100 mg/day or higher were significantly (p less than 0.05) low compared to the respective pretreatment values.(ABSTRACT TRUNCATED AT 250 WORDS)