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(Circulation. 2005;111:2557-2559.)
© 2005 American Heart Association, Inc.

Editorial

Loading, Pretreatment, and Interindividual Variability Issues With Clopidogrel Dosing

Eric R. Bates, MD; Wei C. Lau, MD; Barry E. Bleske, PharmD

From the Division of Cardiovascular Disease, Department of Internal Medicine (E.R.B.), the Department of Anesthesiology (W.C.L.), University of Michigan Medical School, Ann Arbor, and the College of Pharmacy (B.E.B.), University of Michigan, Ann Arbor.

Correspondence to Eric R. Bates, MD, B-1 238 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109. E-mail ebates@umich.edu

Key Words: Editorials • platelets • inhibitors • drugs • pharmacology

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 

Clopidogrel, a thienopyridine, decreases adenosine diphosphate (ADP)–induced platelet aggregation. Clopidogrel is an inactive prodrug that requires in vivo conversion in the liver by the cytochrome P450 (CYP) 3A4 enzyme system to an active metabolite that exerts its antiplatelet effect by noncompetitive inhibition of the platelet ADP receptor subtype P2Y₁₂.¹ The 75-mg once-daily dose was approved by the US Food and Drug Administration (FDA) in November 1997 after the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial² showed superior reduction of adverse cardiovascular events with clopidogrel versus aspirin. The 75-mg once-daily dose had been used in CAPRIE because it produced inhibition of platelet aggregation equivalent to that produced by ticlopidine 250 mg administered twice daily. FDA approval for the 300-mg loading dose in patients with acute coronary syndromes was granted in February 2002 after the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial³ demonstrated a reduction of adverse cardiovascular events with dual antiplatelet therapy versus aspirin. Clopidogrel is not approved by the FDA for adjunctive antiplatelet therapy in percutaneous coronary intervention (PCI), although it has become the standard of care. It is curious that investigations into the optimal loading and maintenance doses of clopidogrel have been pursued only recently.

See p 2560

In this issue of Circulation, Hochholzer et al⁴ performed optical platelet aggregometry and flow cytometry before and after a 600-mg oral dose of clopidogrel in 1001 potential PCI candidates undergoing cardiac catheterization. The findings are consistent with previous observations from small . . . [Full Text of this Article]

Related Article:

Time Dependence of Platelet Inhibition After a 600-mg Loading Dose of Clopidogrel in a Large, Unselected Cohort of Candidates for Percutaneous Coronary Intervention

Willibald Hochholzer, Dietmar Trenk, Devine Frundi, Philipp Blanke, Benjamin Fischer, Katharina Andris, Hans-Peter Bestehorn, Heinz Joachim Büttner, and Franz-Josef Neumann
Circulation 2005 111: 2560-2564. [Abstract] [Full Text]

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