Koike Kaoru
Department of Emergency and Critical Care Medicine, Tohoku University, Graduate School of Medicine.
Nihon Rinsho. 2004 Dec;62(12):2262-6.
Despite promising preclinical evidence, dozens of new anti-sepsis agents have failed to demonstrate clinical efficacy. One of the reasons may be that the preclinical trials were conducted using animal models that did not adequately reflect clinical realities. Various kinds of experiments utilized for the development of new agents were carried where bolus or short term continuous infusions of large doses of bacteria or endotoxin were administered intravenously. For the preclinical testing of agents, (1) i.v. bacteria and endotoxin models in which the total challenge dose of adequate bacteria or endotoxin is reduced and/ or the length of administration time is increased, and (2) peritonitis models, e.g., cecal ligation and puncture and peritoneal implantation of bacteria or endotoxin, will become reasonable choices.
尽管临床前证据很有前景,但数十种新型抗败血症药物未能证明其临床疗效。原因之一可能是临床前试验是使用不能充分反映临床实际情况的动物模型进行的。在开发新药物时进行了各种实验,其中静脉内大剂量推注或短期连续输注细菌或内毒素。对于药物的临床前测试,(1)静脉内细菌和内毒素模型,其中适当细菌或内毒素的总攻击剂量降低和/或给药时间延长,以及(2)腹膜炎模型,例如盲肠结扎和穿刺以及细菌或内毒素的腹膜植入,将成为合理的选择。