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Evaluation of the Pharmacodynamics of Acetylsalicylic Acid 81 mg With or Without Esomeprazole 20 mg in Healthy Volunteers.
- Source :
- American Journal of Cardiovascular Drugs; 2012, Vol. 12 Issue 4, p217-224, 8p, 3 Charts, 2 Graphs
- Publication Year :
- 2012
-
Abstract
- 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 B<subscript>2</subscript> (TXB<subscript>2</subscript>) 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 TXB<subscript>2</subscript> by more than 99.5%. The ratio of suppression of serum TXB<subscript>2</subscript> 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]
- Subjects :
- ANTIULCER drugs
ASPIRIN
BLOOD platelet activation
COMBINATION drug therapy
CONFIDENCE intervals
CROSSOVER trials
HEALTH outcome assessment
REGRESSION analysis
RESEARCH funding
STATISTICAL sampling
THROMBOXANES
PROTON pump inhibitors
TREATMENT effectiveness
DATA analysis software
DESCRIPTIVE statistics
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 11753277
- Volume :
- 12
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- American Journal of Cardiovascular Drugs
- Publication Type :
- Academic Journal
- Accession number :
- 82084587
- Full Text :
- https://doi.org/10.2165/11634280-000000000-00000