Capone Marta L, Tacconelli Stefania, Di Francesco Luigia, Petrelli Maria, Patrignani Paola
Universitàdi Chieti G. d'Annunzio, Sezione di Farmacologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Via dei Vestini, 31, 66013 Chieti, Italy.
Expert Opin Drug Saf. 2008 Jan;7(1):29-42. doi: 10.1517/14740338.7.1.29.
Valdecoxib is an NSAID that is selective for COX-2 (commonly named coxibs). It exhibits anti-inflammatory, analgesic and antipyretic properties in animal models and humans due to inhibition of prostanoid synthesis primarily by affecting COX-2. In this review, the clinical results of cardiovascular effects of valdecoxib and its prodrug parecoxib were analyzed and the information from animal models and clinical pharmacology was exploited, that is, pharmacodynamic and pharmacokinetic data, to give a mechanistic interpretation. Similarly to other coxibs and some traditional (t)NSAIDs less selective for COX-2, such as diclofenac, valdecoxib may increase the risk of thrombotic events through a prostacyclin-based mechanism. The rapid and elevated thrombotic risk detected in two coronary artery bypass graft surgery trials with parecoxib and valdecoxib is coherent with almost complete suppression of COX-2 by supratherapeutic doses (particularly parecoxib), which plausibly translates into a deep suppression of prostacyclin. Drug potency, that is, the degree of suppression of COX-2-dependent prostacyclin, is proposed to represent a strong determinant in the increased incidence of thrombotic events associated with the use of COX-2 inhibitors and some tNSAIDs.
伐地考昔是一种对COX-2具有选择性的非甾体抗炎药（通常称为昔布类）。由于主要通过影响COX-2来抑制前列腺素合成，它在动物模型和人类中表现出抗炎、镇痛和解热特性。在本综述中，分析了伐地考昔及其前体药物帕瑞考昔心血管效应的临床结果，并利用来自动物模型和临床药理学的信息，即药效学和药代动力学数据，进行机制解释。与其他昔布类药物以及一些对COX-2选择性较低的传统非甾体抗炎药（t-NSAIDs）（如双氯芬酸）类似，伐地考昔可能通过基于前列环素的机制增加血栓形成事件的风险。在两项使用帕瑞考昔和伐地考昔的冠状动脉搭桥手术试验中检测到的快速且升高的血栓形成风险，与超治疗剂量（尤其是帕瑞考昔）几乎完全抑制COX-2一致，这可能导致前列环素的深度抑制。药物效力，即对COX-2依赖性前列环素的抑制程度，被认为是与使用COX-2抑制剂和一些t-NSAIDs相关的血栓形成事件发生率增加的一个重要决定因素。
