Long-term activity of clopidogrel: A three-month appraisal in healthy volunteers

The pharmacological effects of clopidogrel, administered once daily at a do se of 75 mg for 12 weeks, were monitored in a group of 35 healthy male subj ects. The maximum intensity of platelet aggregation induced by 5 mu M of AD P and the velocity of aggregation were determined before treatment, and at regular intervals during and after treatment. The long-term effect of clopi dogrel on ADP-induced platelet aggregation was analyzed by comparing maximu m aggregation intensities at baseline, at steady state (average for days 8, 10, and 12), and at week 12, The percent inhibition in maximum intensity f rom baseline was calculated for each time point, A paired, one-tailed Stude nt's t-test was used to test for a change of less than 10% in the maximum i ntensity of platelet aggregation from steady state to week 12, Bleeding tim e was measured before treatment, on four occasions during treatment, and at follow-up. A sustained inhibition of platelet aggregation was observed fro m week 1 through the remainder of the 12-week treatment period, with return to baseline within 2 weeks after the end of treatment, Mean percent inhibi tion was 43 +/- 11.6% (+/-SD) at steady state and 39 +/- 17% at week 12, Th e difference in mean maximum intensity of aggregation between steady state and week 12, 3.28% (95% Cf: [-1.46, 8.01]), was significantly less than the specified limit of 10% (p < 0.001), No statistically significant differenc e between these two time points was observed for the velocity of aggregatio n. The bleeding time prolongation factor during treatment remained stable a t 2,1, These results indicate that the activity of clopidogrel on the inhib ition of platelet aggregation was maintained with long-term treatment.