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)