EFFECTS OF CLOPIDOGREL AND ITS INACTIVE FORM, SR-25989, ON PLASMA, LIVER AND PLATELET LIPIDS IN THE RAT

The aim of the present study was to determine whether clopidogrel, one of the most potent antiplatelet compounds in vivo, could alter the li pid composition of plasma, liver tissue or platelet membranes in the r at. Animals treated (10 mg/kg per day for 7 days) with clopidogrel and its inactive analogue (R form, SR 25989) were compared with control a nimals, Neither compound altered plasma concentrations of triglyceride s or free and esterified cholesterol, and no changes mere observed in liver lipids, Clopidogrel treatment significantly lowered platelet cho lesterol content and cholesterol to phospholipid ratio, while SR 25989 had comparatively smaller effects, Concerning platelet phospholipids, clopidogrel treatment reduced phosphatidylcholine (PC) but increased sphingomyelin (SP) content, whereas SR 25989 lowered PC and phosphatid ylserine (PS) but raised phosphatidylethanolamine (PE) content. A sign ificant increase in the arachidonic acid content of PE was observed on ly in the SR 25989 group, Clopidogrel and SR 25989 both induced an inc rease in the unsaturation level of platelet PC, accompanied by a decre ase in the level of unsaturation in platelet SP, while a similar decre ase was observed for phosphatidylinositol only in the clopidogrel grou p, These changes in platelet membrane composition in the clopidogrel g roup are probably unrelated to the antiaggregating properties of the d rug, but could influence other platelet functions under long-term trea tment.