Clopidogrel antiplatelet activity is independent of age and presence of atherosclerosis

The pharmacodynamic and pharmacokinetic effects of clopidogrel 75 mg taken once daily in the morning before breakfast for 10 days were compared among three groups: 12 healthy young subjects, 10 healthy elderly subjects (>65 years) and 10 otherwise healthy elderly subjects with atherosclerosis, manifested by intermittent claudication. Platelet aggregation induced by 5 microM of ADP was measured in plasma samples taken at screening, 2 hours after dosing on day 1 to day 9; 2, 5, and 24 hours after dosing on day 10; and on alternate days until day 24. The inhibition of platelet aggregation was expressed as the percent reduction in maximum platelet aggregation with respect to baseline. The bleeding time was measured at screening, 5 hours after dosing on day 10, and on day 18. Plasma concentrations of SR26334, the main circulating metabolite of clopidogrel, were determined before dosing on day 1 to day 10 and at regular intervals over 72 hours after dosing on day 10. Inhibition of platelet aggregation appeared 2 hours after the first dose, became significant after the second dose, and progressed to a steady-state value of 55 to 57% by day 7 in the three groups, with no statistically significant difference between groups. A moderate, statistically significant prolongation of bleeding time of similar extent (prolongation factor of 1.5 to 1.6) was found on day 10 in the three groups. The pharmacodynamic parameters generally returned to baseline within 8 days after treatment. Based on AUC(0-24th) values, drug exposures were very similar for the two groups of elderly subjects but approximately twice that for the young group. The pharmacodynamic effects of clopidogrel were comparable in all three groups.