Abstract 3645: Omeprazole, A Potent Cyp 2c19 Inhibitor, Does Not Alter The Pharmacokinetics Or Platelet Aggregation Of Asa And Dipyridamole In Combination

Antiplatelet therapies such as aspirin (ASA), clopidogrel or a combination of ASA and extended-release dipyridamole (ASA/DP) are recommended therapeutic options for reducing the risk of stroke in patients with prior stroke or TIA. The clinical benefit of clopidogrel is highly dependent on the bioactivation of clopidogrel to its active metabolite by CYP 2C19. Omeprazole (OME), a frequently used gastric acid suppressant, is a potent inhibitor of CYP2C19, and has been identified as having a clinically significant interaction with clopidogrel. It was unclear whether ASA/DP would be subject to the same interaction risk when concomitantly administered with OME. This study formally tests whether multiple daily doses of OME 80 mg alters the pharmacokinetics of dipyridamole or the inhibition of platelet aggregation (IPA) of ASA/DP. This study was performed in 60 healthy volunteers as a multiple-dose, open-label, randomized, crossover trial with 4 treatments within 2 treatment sequences. The endpoints included the steady-state Cmax and AUC of DP as well as IPA at 4 and 12 hours postdose. The mean plasma DP concentration time profile for all treatments is displayed in Figure 1. The 90% confidence interval for DP Cmax and AUC was fully contained within 80-125% bounds indicating no clinically significant interaction between ASA/DP and OME. Moreover, concomitant administration of ASA/DP with OME had no effect on the inhibition of arachidonic acid induced platelet aggregation over the normal dosing interval at steady-state (Table 1). There was no difference detected regardless of whether subjects were pre-treated with OME alone or ASA/DP and OME. In conclusion, concurrent administration of OME with ASA/DP does not alter the steady-state pharmacokinetics of DP nor the inhibition of platelet aggregation of ASA/DP, regardless of the order of treatment administration. All treatments were well tolerated. [Table 1.]