Evaluation of the Pharmacodynamics of Acetylsalicylic Acid 81 mg With or Without Esomeprazole 20 mg in Healthy Volunteers.

Background: The absence of a pharmacokinetic interaction between the proton pump inhibitor esomeprazole (40 mg) and acetylsalicylic acid (aspirin, ASA; 325 mg) has previously been established. Objective: This study set out to investigate the potential for pharmacodynamic interaction between low-dose ASA and esomeprazole in healthy volunteers, by measuring ASA antiplatelet activity. Study Design: This was a single-center, open-label, two-period, randomized crossover study. Participants: Healthy male and female volunteers aged 18-75 years were included. All volunteers received ASA 81 mg once daily for 5 days prior to the study (pre-screen). Subjects were eligible for inclusion if they had aspirin reactivity units (ARU, as measured by the VerifyNow ASA assay) of <550 on Day 6. Intervention: After pre-screening and a washout period of at least 14 days, eligible volunteers received ASA 81 mg with or without esomeprazole 20 mg once daily for 5 days in randomized order, with a 14-day washout between treatments. Main Outcome Measure: The main outcome measure was the antiplatelet activity of ASA, as assessed by ARU ratio relative to baseline in the VerifyNow ASA assay; suppression of serum thromboxane B₂ (TXB₂) was a secondary endpoint. Statistical comparisons were made using linear mixed models. Results: A total of 29 volunteers (19 aged ≥50 years; 8 women; 21 men) were evaluable for pharmacodynamic analysis (per protocol). All volunteers on both treatments achieved ARU<550 at Day 6. The geometric mean ratio of D ay 6 to D ay 1 (baseline) platelet aggregation was 0.70 (95 % confidence interval [CI] 0.68, 0 .72) with ASA alone and 0.71 (95% CI 0.69, 0. 74) with ASA + esomeprazole. The ratio of platelet aggregation (ASA + esomeprazole /ASA) was 1.02 (95 % CI 0.99, 1.05). ASA administered alone or with esomeprazole reduced serum TXB₂ by more than 99.5%. The ratio of suppression of serum TXB₂ levels (ASA + esomeprazole / ASA) was 1.06 (95% CI 0.88, 1.29). The combination of ASA and esomeprazole was well tolerated. Conclusion: No pharmacodynamic interaction between low-dose ASA and esomeprazole was found with regard to platelet function. Trial Registration: Registered at ClinicalTrials. gov as NCT01199328. [ABSTRACT FROM AUTHOR]