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

The pharmacological effects of clopidogrel, administered once daily at a dose of 75 mg for 12 weeks, were monitored in a group of 35 healthy male subjects. The maximum intensity of platelet aggregation induced by 5 microM of ADP and the velocity of aggregation were determined before treatment, and at regular intervals during and after treatment. The long-term effect of clopidogrel on ADP-induced platelet aggregation was analyzed by comparing maximum aggregation intensities at baseline, at steady state (average for days 8, 10, and 12), and at week 12. The percent inhibition in maximum intensity from baseline was calculated for each time point. A paired, one-tailed Student's t-test was used to test for a change of less than 10% in the maximum intensity of platelet aggregation from steady state to week 12. Bleeding time was measured before treatment, on four occasions during treatment, and at follow-up. A sustained inhibition of platelet aggregation was observed from 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 inhibition was 43+/-11.6% (+/-SD) at steady state and 39+/-17% at week 12. The difference in mean maximum intensity of aggregation between steady state and week 12, 3.28% (95% CI: [-1.46, 8.01]), was significantly less than the specified limit of 10% (p <0.001). No statistically significant difference between these two time points was observed for the velocity of aggregation. The bleeding time prolongation factor during treatment remained stable at 2.1. These results indicate that the activity of clopidogrel on the inhibition of platelet aggregation was maintained with long-term treatment.