55191
document
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 B ( 2 ) ( TXB ( 2 ) ) 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 Day 6 to Day 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 ( 2 ) by more than 99.5 % . The ratio of suppression of serum TXB ( 2 ) 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 .
55192
Intervention_Pharmacological
ASA 81 mg
55193
Intervention_Pharmacological
aspirin
55194
Intervention_Pharmacological
ASA 81 mg
55195
Intervention_Pharmacological
esomeprazole 20 mg
55196
Outcome_Other
Evaluation
55197
Outcome_Physical
pharmacokinetic interaction
55198
Outcome_Physical
pharmacodynamic interaction
55199
Outcome_Physical
antiplatelet activity
55200
Outcome_Physical
aspirin reactivity units
55201
Outcome_Other
( ARU , as measured by the VerifyNow ASA assay )
55202
Outcome_Physical
antiplatelet activity of ASA , as assessed by
55203
Outcome_Other
ARU ratio relative to baseline in the VerifyNow ASA assay
55204
Outcome_Physical
suppression of serum thromboxane B ( 2 ) ( TXB ( 2 ) )
55205
Participant_Condition
healthy volunteers .
55206
Participant_Age
Healthy male and female volunteers aged 18-75 years were included .