In-vitro Drug Interaction of Clopidogrel with Omeprazole and Lansoprazole

Abstract

Atherosclerotic cardiovascular disease is very common worldwide. Clopidogrel is prescribed for chronic use in these patients. Clopidogrel is a prodrug and a adenosine diphosphate (ADP) receptor inhibitors. Its active metabolite act on P2Y12 Receptor which is a G-Protein coupled receptor and it inhibits the process of initiation of platelet aggregation. Omeprazole and lansoprazole are the proton pump inhibitors which are mostly prescribed in combination with clopidogrel to reduce gastric bleeding. There were no studies done to elucidate the changes in metabolic clearance profile of clopidogrel in combination with either omeprazole or lansoprazole in rat liver microsomes. Pharmacokinetics is the mathematical analysis of ADME. For this study prepared pooled liver microsomes from Sprague Dawley rat for used as a valuable in-vitro model to elucidate biotransformation mechanism of new chemical entity and drug-drug interaction by different methods and standardize the prepared rat liver microsomes with respect to commercially available Xenotech’s rat liver microsomes. Metabolism, clearance and elimination rate constant of clopidogrel was significantly decreased when it was co-incubated with omeprazole as compared to co-incubation with lansoprazole but half life of clopidogrel was significantly increased when it was co-incubated with omeprazole as compared to co-incubation with lansoprazole. So lansoprazole is better to prescribe as a co-administration therapy with clopidogrel.