Clinical Bioequivalence of a Dose of Clopidogrel Leti Cravid Tablets 75 mg Versus Clopidogrel Sanofi Plavix Tablets 75 mg Administered on a Daily Dose for 7 Days on Healthy Volunteers: A Clinical Trial Aixa Mu ¨ ller, MD, 1 Jose ´ Octavio, MD, 1 Marı ´a Y. Gonza ´ lez, MD, 2 * Jesu ´ s Contreras, MD, 2 Gisela Me ´ndez, MgSc, 2 Milagros Portillo, MgSc, 2 and Zuleima Valero, MgSc 2 Patients undergoing percutaneous coronary intervention procedures, as in patients with coronary disease, should receive treatment indefinitely with acetylsalicylic acid and clopidogrel. New brands of clopidogrel have been developed at lower costs, for helping to avoid premature suspension of antiplatelet therapy, as Cravid Leti Laboratories clopidogrel. Its effectiveness and safety must be compared with Plavix international standard. A prospective, comparative, cross-over, and randomized study was conducted in healthy volunteers. Each group received 1 tablet of Clopidogrel Leti or Clopidogrel Sanofi, 75 mg in a single dose daily for 7 days, followed by 7-day washout period before administration of second treatment. Platelet aggregation was measured at the start of each period and at 7 days of treatment through optical aggregometry, using an optical aggregometer 490- 2D Chrono-Log, with a self-calibration system working with platelet-rich plasma with readings 0%– 100% of light transmission. An important decrease of platelet aggregation was observed in both groups at 7 days of treatment of more than 50%, independent of adenosine diphosphate reactive (Helena and Chrono-Log) used for aggregation (P , 0.05). The relationship between the mean and 90% confidence interval ratio obtained with the 2 different adenosine diphosphate brands were between 80% and 125%, therefore, it can be considered that both brands are bioequivalent and perfectly exchangeable. Keywords: clopidogrel, pharmacodynamic bioequivalence, platelet aggregation INTRODUCTION Clopidogrel is an oral antiplatelet therapy indicated to prevent myocardial infarction, ictus, and vascular death in patients with recent history of stroke, heart, or perivascular disease. Clopidogrel is inactive in vitro and exerts its effects as platelet antiaggregant through liver activation. Its active metabolite inhibits selectively and irreversibly adenosine diphosphate (ADP)–induced platelet aggre- gation, blocking the binding of ADP to its platelet receptor, altering the activation of the glycoprotein GIIb/IIIa complex. Because this complex is the most important receptor for fibrinogen, its inactivation blocks the binding of fibrinogen to platelets, which finally inhibits platelet aggregation. Because-clopidogrel active metabolite irreversibly modifies the platelet receptor, platelets exposed to the drug remain altered for the remainder of their lives. Clopidogrel-active 1 Central University of Venezuela, National Institute of Hematol- ogy and Oncology, Caracas, Venezuela; and 2 Leti Laboratories, Department of Clinical Investigation, Guarenas, Venezuela. *Address for correspondence: Leti Laboratories, Clinical Investi- gation Department, 2nd Avenue, Sector 3, Block J, Guarenas, 1722, Venezuela. E-mail: mgonzalez@leti.com.ve American Journal of Therapeutics 17, 351–356 (2010) 1075–2765 Ó 2010 Lippincott Williams & Wilkins www.americantherapeutics.com