Methods: Twenty one coronary artery disease patients of both genders who expressed willingness to participate underwent screening, randomized equally into two cross-over sequences, dosed with clopidogrel and clopidogrel + esomeprazole in respective periods. Blood samples were collected through ante-cubital or forearm vein indwelling catheter. Concentration of clopidogrel parent prodrug in isolated plasma was determined using validated sensitive liquid chromatography – mass spectrometry. Pharmacokinetic modelling was carried out using PKSOLVER add in for Microsoft Excel. Results: The pharmacokinetic profile of clopidogrel was non-significantly altered by esomeprazole. Statistically significant difference in peak plasma concentration, apparent volume of distribution and clearance of clopidogrel was observed only during period II in subjects co-dosed with esomeprazole (P Value = 0.0483, 0.0011 and 0.0015 respectively). All other primary and secondary pharmacokinetic parameters displayed minor alterations during either periods (P value<0.05). Conclusion: The non-significant alteration of clopidogrel pharmacokinetics by esomeprazole can be potentiated by underlying predisposing factors such as presence of CYP2C19 allelic variants, increasing the risk of cardiovascular events. Hence co-administration of clopidogrel and esomeprazole should be under clinical monitoring and is not recommended in poor responders of anti-platelet therapy with clopidogrel.
