Noble S, McTavish D
Adis International Limited, Auckland, New Zealand.
Drugs. 1996 Oct;52(4):589-605. doi: 10.2165/00003495-199652040-00012.
Reteplase (BM 06.022; r-PA) is a recombinant peptide which consists of the kringle 2 and protease domains of human tissue-type plasminogen activator. It has been developed as a thrombolytic treatment for acute myocardial infarction (AMI). The half-life of reteplase allows administration as a double-bolus injection (second injection given 30 minutes after the first) rather than by the prolonged and, in some cases, more complex intravenous infusion regimens that are required for most other thrombolytic agents. Reteplase produced rapid and effective coronary artery thrombolysis in a number of dose-finding and comparative studies. Double-bolus administration of reteplase 10U + 10U produced significantly higher coronary artery patency rates than accelerated alteplase (100mg as a 1.5-hour infusion) in patients with AMI in the RAPID-II study. The 10U + 10U reteplase regimen produced a 35-day survival rate at least equivalent to that seen with a 1-hour infusion of streptokinase 1.5 million units in 5986 patients in the INJECT study, which was designed to demonstrate equivalence between treatments. As with other thrombolytics, bleeding was the most common adverse event seen in reteplase recipients. No significant differences in the overall risk of haemorrhage were observed between reteplase and either accelerated alteplase or standard streptokinase treatment in clinical trials. The risk of stroke in reteplase recipients appears to be similar to that for other thrombolytic agents [1.2% incidence in 3288 patients treated with reteplase 10U + 10U in clinical trials (0.76% for haemorrhagic stroke)], although accurate statistical assessment of the relative risk is not possible for the data available to date. Thus, reteplase is an effective thrombolytic agent which can be administered as a double-bolus injection regimen rather than as a prolonged infusion. Together with acquisition cost and general pharmacoeconomic data (which are not yet available), the results of GUSTO-III (a trial comparing double-bolus reteplase with accelerated alteplase in 15 000 patients) will have a major influence on the pattern of use of reteplase. In the meantime, data from the available clinical trials suggest that reteplase is a fast-acting and effective thrombolytic treatment for patients with AMI.
瑞替普酶（BM 06.022；r-PA）是一种重组肽，由人组织型纤溶酶原激活剂的kringle 2和蛋白酶结构域组成。它已被开发用于急性心肌梗死（AMI）的溶栓治疗。瑞替普酶的半衰期允许采用双剂量推注给药（第一次注射后30分钟给予第二次注射），而不是采用大多数其他溶栓剂所需的延长的、在某些情况下更为复杂的静脉输注方案。在一些剂量探索和对比研究中，瑞替普酶能迅速有效地实现冠状动脉溶栓。在RAPID-II研究中，对于AMI患者，瑞替普酶10U + 10U双剂量推注给药产生的冠状动脉通畅率显著高于加速给药的阿替普酶（100mg，1.5小时输注）。在INJECT研究中，旨在证明不同治疗方法等效性的5986例患者中，10U + 10U瑞替普酶给药方案产生的35天生存率至少等同于150万单位链激酶1小时输注的生存率。与其他溶栓剂一样，出血是接受瑞替普酶治疗的患者中最常见的不良事件。在临床试验中，未观察到瑞替普酶与加速给药的阿替普酶或标准链激酶治疗在出血总体风险上存在显著差异。接受瑞替普酶治疗的患者发生中风的风险似乎与其他溶栓剂相似[在临床试验中，3288例接受10U + 10U瑞替普酶治疗的患者中风发生率为1.2%（出血性中风为0.76%）]，尽管就目前可得数据而言，无法对相对风险进行准确的统计学评估。因此，瑞替普酶是一种有效的溶栓剂，可采用双剂量推注给药方案而非延长输注给药。连同购置成本和一般药物经济学数据（目前尚未可得）一起，GUSTO-III（一项在15000例患者中比较双剂量推注瑞替普酶与加速给药阿替普酶的试验）的结果将对瑞替普酶的使用模式产生重大影响。与此同时，现有临床试验数据表明，瑞替普酶对于AMI患者是一种起效迅速且有效的溶栓治疗药物。
