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 lipid composition of plasma, liver tissue or platelet membranes in the rat. Animals treated (10 mg/kg per day for 7 days) with clopidogrel and its inactive analogue (R form, SR 25989) were compared with control animals. Neither compound altered plasma concentrations of triglycerides or free and esterified cholesterol, and no changes were observed in liver lipids. Clopidogrel treatment significantly lowered platelet cholesterol 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 phosphatidylserine (PS) but raised phosphatidylethanolamine (PE) content. A significant increase in the arachidonic acid content of PE was observed only in the SR 25989 group. Clopidogrel and SR 25989 both induced an increase in the unsaturation level of platelet PC, accompanied by a decrease in the level of unsaturation in platelet SP, while a similar decrease was observed for phosphatidylinositol only in the clopidogrel group. These changes in platelet membrane composition in the clopidogrel group are probably unrelated to the antiaggregating properties of the drug, but could influence other platelet functions under long-term treatment.
Leray
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INSERM U.311, Biologie et pharmacologie des interactions dusang avec les vaisseaux et les biomatériaux, Etablissement de Transfusion Sanguine, 10 rue Spielmann, B. P. 36, 67065 Strasbourg Cédex, France.
Freund
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Wiesel
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Gutbier
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Cazenave
J P
JP
Gachet
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