Circulation. 2005;112:2946-2950
Published online before print October 31, 2005, doi: 10.1161/CIRCULATIONAHA.105.559088
Published online before print October 31, 2005, doi: 10.1161/CIRCULATIONAHA.105.559088
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(Circulation. 2005;112:2946-2950.)
© 2005 American Heart Association, Inc.
Interventional Cardiology |
Absorption, Metabolization, and Antiplatelet Effects of 300-, 600-, and 900-mg Loading Doses of Clopidogrel
Results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial
From Deutsches Herzzentrum, Technische Universität München, Munich (N.v.B., G.P.-M., A.K., A.S.), and Institut für Pharmakologie, Klinikum der Universität zu Köln, Cologne (D.T., E.S.), Germany.
Correspondence to Dr Nicolas von Beckerath, Deutsches Herzzentrum München Lazarettstr 36, 80636 München, Germany. E-mail beckerath{at}dhn.mhn.de
Received April 28, 2005; revision received August 12, 2005; accepted August 15, 2005.
Background— For patients undergoing percutaneous coronary intervention, the administration of a clopidogrel loading dose ranging from 300 to 600 mg is currently recommended. It is unknown, though, whether loading doses higher than 600 mg exert additional suppression of platelet function.
Methods and Results— Sixty patients with suspected or documented coronary artery disease admitted to our hospital for coronary angiography were included in this trial. They were allocated to 1 of 3 clopidogrel loading doses (300, 600, or 900 mg) in a double-blinded, randomized manner. Plasma concentrations of the active thiol metabolite, unchanged clopidogrel, and the inactive carboxyl metabolite of clopidogrel were determined before and serially after drug administration. Optical aggregometry was performed before and 4 hours after administration of clopidogrel. Loading with 600 mg resulted in higher plasma concentrations of the active metabolite, clopidogrel, and the carboxyl metabolite compared with loading with 300 mg (P
0.03) and lower values for adenosine diphosphate-induced (5 and 20 µmol/L) platelet aggregation 4 hours after drug administration (P=0.01 and 0.004). With administration of 900 mg, no further increase in plasma concentrations of active metabolite and clopidogrel (P
0.38) and no further suppression of adenosine diphosphate-induced (5 and 20 µmol/L) platelet aggregation 4 hours after drug administration was achieved when compared with administration of 600 mg (P=0.59 and 0.39).
Conclusions— Single doses of clopidogrel higher than 600 mg are not associated with an additional significant suppression of platelet function because of limited clopidogrel absorption.
Key Words: platelets • pharmacology • receptors • pharmacokinetics
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