Clopidogrel bioavailability: absence of influence of food or antacids

Two open, randomized, crossover bioavailability studies were carried out to assess the influence of concurrent antacid medication and food on the bioavailability of clopidogrel. A fed/fasting study was conducted in 12 elderly male subjects. Each subject took a single 75 mg dose of clopidogrel on two occasions-in the morning after an overnight fast, either during a standardized breakfast, or with breakfast delayed by 4 hours after dosing. A washout period of 7 days was observed between the two dosings. Twelve healthy male subjects participated in the antacid study. They fasted overnight and for 4 hours after dosing and took a single 75 mg dose of clopidogrel at 8:00 a.m. on two occasions separated by a washout period of 14 days. For one dose, Maalox 2 x 400 mg tablets were taken 1 hour before the clopidogrel dose. Pharmacokinetic parameters of SR26334, the main circulating metabolite of clopidogrel, were derived from plasma concentrations of the latter compound determined before and at regular intervals over 36 hours after dosing. For the fed/fasting study, mean Cmax values (+/-SD) were 2.7+/-0.62 mg/L and 2.1+/-0.96 mg/L for the fasting state and the fed state, respectively and the 90% CI of Cmax ratio was [0.57 - 0.97]. Mean AUC(0-obs) values (AUC to the last observed value) were 7.1+/-1.6 mg.h/L and 7.4+/-1.64 mg.h/L, respectively, and the 90% Cl of AUC ratios were [0.90 - 1.02] and [0.89 - 0.97], respectively. For the antacid study, mean Cmax values were 2.6+/-0.84 mg/L and 2.5+/-0.87 mg/L for the no-antacid regimen and the antacid regimen, respectively, and the 90% CI of Cmax ratio was [0.74 - 1.16]. Mean AUC(0-obs) values were 6.3+/-1.34 mg.h/L and 5.8+/-1.33 mg.h/L, respectively, and the 90% CI of AUC ratios was [0.89+/-0.97]. Thus, exposure to SR26334, and therefore net absorption of clopidogrel, was not significantly modified by food or by prior antacid ingestion.