on October 31, 2005
Circulation. 2005
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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Submitted on April 28, 2005
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. * To whom correspondence should be addressed. E-mail: beckerath{at}dhn.mhn.de.
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 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.
Revised on August 12, 2005
Accepted on August 15, 2005
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
Nicolas von Beckerath MD*,
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).
Key words: platelets • pharmacology • receptors • pharmacokinetics
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Circulation 2005 112: 2887.
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H. Hamdalla and S. R. Steinhubl Clinical efficacy of clopidogrel across the whole spectrum of indications: percutaneous coronary intervention Eur. Heart J. Suppl., October 1, 2006; 8(suppl_G): G20 - G24. [Abstract] [Full Text] [PDF]
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D. J. Kereiakes and E. M. Antman Clinical Guidelines and Practice: In Search of the Truth J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1129 - 1135. [Abstract] [Full Text] [PDF]
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G. Montalescot, G. Sideris, C. Meuleman, C. Bal-dit-Sollier, N. Lellouche, Ph. G. Steg, M. Slama, O. Milleron, J.-P. Collet, P. Henry, et al. A Randomized Comparison of High Clopidogrel Loading Doses in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes: The ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) Trial J. Am. Coll. Cardiol., September 5, 2006; 48(5): 931 - 938. [Abstract] [Full Text] [PDF]
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R. P. Giugliano and E. Braunwald The Year in Non-ST-Segment Elevation Acute Coronary Syndromes J. Am. Coll. Cardiol., July 18, 2006; 48(2): 386 - 395. [Full Text] [PDF]
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S. R. Dixon, C. L. Grines, and W. W. O'Neill The Year in Interventional Cardiology J. Am. Coll. Cardiol., April 18, 2006; 47(8): 1689 - 1706. [Full Text] [PDF]
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 A. Kastrati, J. Mehilli, F.-J. Neumann, F. Dotzer, J. ten Berg, H. Bollwein, I. Graf, M. Ibrahim, J. Pache, M. Seyfarth, et al. Abciximab in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention After Clopidogrel Pretreatment: The ISAR-REACT 2 Randomized Trial JAMA, April 5, 2006; 295(13): 1531 - 1538. [Abstract] [Full Text] [PDF]
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T. H. Wang, D. L. Bhatt, and E. J. Topol Aspirin and clopidogrel resistance: an emerging clinical entity Eur. Heart J., March 2, 2006; 27(6): 647 - 654. [Abstract] [Full Text] [PDF]
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