Omeprazole coadministration decreased clopidogrel active metabolite AUC by 40-47% (P≤0.002) and increased platelet aggregation, whereas pantoprazole showed no significant interaction.
RCT (n=282)
Placebo-controlled
Crossover
Does coadministration of omeprazole or pantoprazole reduce the pharmacokinetic and pharmacodynamic efficacy of clopidogrel in healthy subjects?
Omeprazole, but not pantoprazole, significantly attenuates the pharmacokinetic and pharmacodynamic effects of clopidogrel, suggesting pantoprazole may be a safer PPI choice for patients requiring clopidogrel.
valor p: p=≤ 0.002
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 AUC(0-24) of the clopidogrel active metabolite H4 by 40, 47, 41, and 14% (P ≤ 0.002), respectively; increased maximal platelet aggregation (MPA) induced by 5 micromol/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.
Angiolillo et al. (Wed,) conducted a rct in Healthy subjects (n=282). Omeprazole or Pantoprazole coadministered with Clopidogrel vs. Clopidogrel alone was evaluated on AUC(0-24) of the clopidogrel active metabolite H4 (p=≤ 0.002). Omeprazole coadministration decreased clopidogrel active metabolite AUC by 40-47% (P≤0.002) and increased platelet aggregation, whereas pantoprazole showed no significant interaction.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: