Clopidogrel does not affect the pharmacokinetics of theophylline

The potential influence of clopidogrel on the pharmacokinetics of theophyll ine was evaluated in 15 healthy male subjects during the pharmacokinetic st eady state of theophylline, after single and multiple doses. Theophylline w as administered orally as one 300-mg capsule in the morning before breakfas t and one in the evening before dinner for 13 days (day 1 through day 13), and one capsule on the morning of day 14. Clopidogrel was administered oral ly as one 75-mg tablet in the morning before breakfast from day 5 through d ay 14. Plasma concentration of theophylline was determined at the following times: before the morning dose on days, 1, 6-9, and 12; before administrat ion, then at 0.5, 1,2, 3, 4, 5, 6, 7, 8, 10, and 12 hours after administrat ion on days 4, 5, and 14. Tests of hemostasis (ADP-induced platelet aggrega tion and bleeding time) were carried out 2 hours after clopidogrel dosing o n days 5, 7, 9, 11, and 14. The curves of the mean plasma concentration of theophylline over 12 hours post-morning dose on day 4 (drug alone), day 5 ( after a single dose of clopidogrel), and day 14 (after 10 days of clopidogr el coadministration) were superimposable, indicating the absence of an effe ct of clopidogrel on the steady-state pharmacokinetics of theophylline. The re were no statistically significant differences between the days of admini stration for the log-transformed values of theophylline C-bt (concentration before treatment) C-max, AUC(0-12h), and C-min; and the 90% confidence int ervals of the day 5/day 4, day 14/day 4, and day 14/day 5 ratios of the geo metric means of C-bt all fell within the (0.80; 1.25) interval. These resul ts show that the administration of clopidogrel during steady state theophyl line administration had no effect on the plasma concentration of the latter drug. The average steady-state (days 11-14) percentage of inhibition of AD P-induced platelet aggregation by clopidogrel with respect to day 1 was 46% . The geometric mean of the bleeding time prolongation factor was about 2 a t steady state. The latter results indicate that the pharmacodynamics of cl opidogrel were not affected by concomitant theophylline.