drug interaction clopidogrel/plavix and omeprazole/prilosec not clopidogrel and pantoprazole/protonix

drug interaction clopidogrel/plavix and omeprazole/prilosec not clopidogrel and pantoprazole/protonix

The results suggest that a metabolic drug–drug interaction exists between clopidogrel and omeprazole but not between clopidogrel and pantoprazole.

Omeprazole (Brand names: Losec, Omesec, Prilosec, UlcerGard, Zegerid)
Pantoprazole (Brand name: Protonix)

Amplify’d from www.nature.com

Clinical Pharmacology & Therapeutics (2010); advance online publication 15 September 2010. doi:10.1038/clpt.2010.219

Differential Effects of Omeprazole and Pantoprazole on the Pharmacodynamics and Pharmacokinetics of Clopidogrel in Healthy Subjects: Randomized, Placebo-Controlled, Crossover Comparison Studies

D J Angiolillo1, C M Gibson2, S Cheng3, C Ollier4, O Nicolas4, L Bergougnan5, L Perrin6, F P LaCreta7, F Hurbin4 and M Dubar5

Abstract

Four randomized, placebo-controlled, crossover studies were conducted among 282 healthy subjects to investigate whether an interaction exists between clopidogrel (300-mg loading dose/75-mg/day maintenance dose) and the proton-pump inhibitor (PPI) omeprazole (80 mg) when they are administered simultaneously (study 1); whether the interaction, if any, can be mitigated by administering clopidogrel and omeprazole 12 h apart (study 2) or by increasing clopidogrel to 600-mg loading/150-mg/day maintenance dosing (study 3); and whether the interaction applies equally to the PPI pantoprazole (80 mg) (study 4). Relative to levels after administration of clopidogrel alone in studies 1,2,3, and 4, coadministration of PPI decreased the AUC0–24 of the clopidogrel active metabolite H4 by 40, 47, 41, and 14% (P ≤ 0.002), respectively; increased maximal platelet aggregation (MPA) induced by 5 µmol/l adenosine diphosphate (ADP) by 8.0, 5.6, 8.1, and 4.3% (P ≤ 0.014), respectively; and increased the vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) by 20.7, 27.1, 19.0 (P < 0.0001), and 3.9% (P = 0.3319), respectively. The results suggest that a metabolic drug–drug interaction exists between clopidogrel and omeprazole but not between clopidogrel and pantoprazole.

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