Estimation of Clinical Pharmacokinetic Interaction between Atorvastatin and Clopidogrel in Atherosclerotic Heart Disease Patients

Atherosclerotic heart disease includes acute coronary syndromes and hyperlipidmia. The prescription of patients with atherosclerotic heart disease mostly contains atorvastatin and clopidogrel. Aim of this study is to estimate clinical pharmacokinetic interaction between atorvastatin and clopidogrel in atherosclerotic heart disease patients. This study was conducted by estimating the carboxylic acid clopidogrel metabolite level in blood serum and estimating the effect of atorvastatin on blood serum level of clopidogrel metabolite level. In this non randomized, prospective, crossover, single centric and open labelled study was carried out on patients (n=11) of atherosclerotic heart disease with or without PCI. Blood samples were collected, on the basis of pharmacokinetic drug profile, after 1 hr of dosing of clopidogrel. After 24 hr blood samples were collected after 1hr of dosing of clopidogrel with atorvastatin. Serum was separated and stored at -40 °c until analysis. Estimation of carboxylic acid metabolite of clopidogrel was carried out by using validated and sensitive HPLC method. Concentration of carboxylic acid clopidogrel metabolite was observed significantly increased (p<0.05) in patients treated with clopidogrel and atorvastatin (7.02 ± 0.86 μg/ml) as compared to patients treated with clopidogrel alone (6.20 ± 0.91 μg/ml). Analysis revealed prominent increases in concentration of clopidogrel carboxylic acid metabolite in presence of atorvastatin and clopidogrel. This might be due to the inhibition of intestinal P-glycoprotein function by atorvastatin and so clopidogrel efflux was reduced. This might have led to increased concentration of clopidogrel in systemic circulation.