Mousa Shaker A
Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208-3492, USA.
Cardiovasc Drug Rev. 2002 Fall;20(3):199-216. doi: 10.1111/j.1527-3466.2002.tb00087.x.
Standard unfractionated heparin (UFH) has been in clinical use for over 50 years. The commercial use of low molecular weight heparins (LMWHs) began in the mid 1980s for hemodialysis and the prophylaxis of deep vein thrombosis (DVT). Initially, the clinical development of LMWHs was concentrated on the European continent. Subsequently, LMWHs were introduced in North America as well. In the initial stages of development of these drugs only nadroparin, dalteparin and enoxaparin were used. Subsequently, several other LMWHs such as ardeparin, tinzaparin, reviparin and parnaparin were introduced. LMWHs constitute a group of important medications with total sales reaching nearly 2.5 billion dollars with expanded indications reaching far beyond the initial indications for the prophylaxis of post-surgical DVT. This review highlights the pharmacology of tinzaparin. Unlike other LMWHs, tinzaparin is prepared by enzymatic hydrolysis with heparinase, while various chemical depolymerization methods are used for the synthesis of other LMWHs. As compared with the standard heparin, LMWHs have different pharmacodynamic, and pharmacokinetic properties; they also differ in clinical benefits.
标准普通肝素(UFH)已临床应用50多年。低分子量肝素(LMWHs)于20世纪80年代中期开始用于血液透析和预防深静脉血栓形成(DVT)。最初,LMWHs的临床开发集中在欧洲大陆。随后,LMWHs也被引入北美。在这些药物开发的初始阶段,仅使用了那屈肝素、达肝素和依诺肝素。随后,又引入了其他几种LMWHs,如阿地肝素、替扎肝素、瑞肝素和帕肝素。LMWHs是一类重要的药物,总销售额近25亿美元,其适应证扩展远远超出了最初预防术后DVT的适应证。本综述重点介绍替扎肝素的药理学。与其他LMWHs不同,替扎肝素是通过肝素酶酶解制备的,而其他LMWHs的合成则采用各种化学解聚方法。与标准肝素相比,LMWHs具有不同的药效学和药代动力学特性;它们在临床益处方面也有所不同。