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American Journal of Cardiovascular Drugs

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01-06-2014 | Original Research Article

Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers

Authors: Tommy Andersson, Peter Nagy, Mohammad Niazi, Sven Nylander, Hal Galbraith, Santosh Ranjan, Lars Wallentin

Published in: American Journal of Cardiovascular Drugs | Issue 3/2014

Abstract

Objective

The effect of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of clopidogrel was assessed in two healthy volunteer crossover studies.

Subjects and methods

Study 1: subjects received clopidogrel alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for 29 days in three treatment periods (randomized treatment sequence assignment). Study 2: subjects received clopidogrel alone (75 mg/day for 9 days) and clopidogrel alone for 4 days followed by clopidogrel plus fixed-combination esomeprazole 20 mg/low-dose acetylsalicylic acid (ASA) 81 mg for 5 days in two treatment periods (randomized treatment sequence assignment). Pharmacokinetic effects were estimated by measuring active metabolite of clopidogrel, and pharmacodynamic effects by inhibition of adenosine diphosphate (ADP)-induced platelet aggregation.

Results

There was a relative decrease of up to 50 % in exposure to the active metabolite of clopidogrel with the different PPIs (study 1), and close to 40 % with esomeprazole/low-dose ASA (study 2), compared with clopidogrel alone. There was an absolute decrease of up to 17 % in inhibition of ADP-induced platelet aggregation with co-administration of different PPIs, compared with clopidogrel alone; however, no differences in platelet inhibition were observed during co-administration with the esomeprazole/low-dose ASA fixed-dose combination.

Conclusion

Omeprazole, esomeprazole and lansoprazole decreased systemic exposure to the active metabolite of clopidogrel in healthy volunteers, leading to modest decreases in its antiplatelet effect. However, no apparent differences in platelet inhibition were observed when esomeprazole was co-administered with low-dose ASA as a fixed-dose combination.

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Title: Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers
Authors: Tommy Andersson
Peter Nagy
Mohammad Niazi
Sven Nylander
Hal Galbraith
Santosh Ranjan
Lars Wallentin
Publication date: 01-06-2014
Publisher: Springer International Publishing
Published in: American Journal of Cardiovascular Drugs / Issue 3/2014
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI: https://doi.org/10.1007/s40256-014-0073-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers

Abstract

Objective

Subjects and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Subjects and methods

Results

Conclusion

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