有效的可用性,可可靠访问,和负担得起的治疗蛇咬伤envening是一个关键和长期未满足的医疗需求。最近,小,已确定与抗蛇毒血清联合使用的具有口服生物利用度的合成毒素特异性抑制剂具有极大改善蛇咬伤后结局的潜力。Varespladib,一个小,广泛而有效地抑制分泌的磷脂酶A2(sPLA2s)毒液毒素的合成分子由于其在治疗蛇咬伤毒液中的潜在用途而重新引起了对此类抑制剂的兴趣。varespladib及其口服剂型的开发,varespladib-甲基,以前的临床开发活动加速了与溃疡性结肠炎相关的非envenoming病症的治疗,类风湿性关节炎,哮喘,脓毒症,和急性冠脉综合征。迄今为止,29项评估安全性的临床研究,药代动力学(PK),varespladib对非蛇咬伤情况的疗效已经在4600多名人类受试者中完成,这些药物通常具有良好的耐受性,并且被认为在人类中使用是安全的。自2016年以来,超过30种出版物描述了这种结构,函数,varespladib的疗效直接解决了其治疗蛇咬伤的潜力。这篇综述总结了临床前发现,并概述了科学支持,潜在的限制,以及varespladib用作蛇咬伤治疗的下一步发展,目前正在美国和印度进行2期人体临床试验。
The availability of effective, reliably accessible, and affordable treatments for snakebite envenoming is a critical and long unmet medical need. Recently, small, synthetic toxin-specific inhibitors with oral bioavailability used in conjunction with antivenom have been identified as having the potential to greatly improve outcomes after snakebite.
Varespladib, a small, synthetic molecule that broadly and potently inhibits secreted phospholipase A2 (sPLA2s) venom toxins has renewed interest in this class of inhibitors due to its potential utility in the treatment of snakebite envenoming. The development of
varespladib and its oral dosage form,
varespladib-methyl, has been accelerated by previous clinical development campaigns to treat non-envenoming conditions related to ulcerative colitis, rheumatoid arthritis, asthma, sepsis, and acute coronary syndrome. To date, twenty-nine clinical studies evaluating the safety, pharmacokinetics (PK), and efficacy of
varespladib for non-snakebite envenoming conditions have been completed in more than 4600 human subjects, and the drugs were generally well-tolerated and considered safe for use in humans. Since 2016, more than 30 publications describing the structure, function, and efficacy of
varespladib have directly addressed its potential for the treatment of snakebite. This review summarizes preclinical findings and outlines the scientific support, the potential limitations, and the next steps in the development of
varespladib\'s use as a snakebite treatment, which is now in Phase 2 human clinical trials in the United States and India.