Shapiro T A, Were J B, Talalay P, Bueding E, Rocco L, Danso K, Massof R, Green R, Mellits E D, Lietman P S
Am J Trop Med Hyg. 1986 Sep;35(5):945-53. doi: 10.4269/ajtmh.1986.35.945.
Single oral doses of amoscanate (4-isothiocyanato-4'-nitrodiphenylamine), an experimental antiparasitic agent, are highly effective in animals against the four major species of schistosomes which infect humans. Two prospective, randomized, double blinded, placebo controlled Phase I studies were designed to evaluate the tolerance and safety of the 5% aqueous suspension of 2-mu particles of amoscanate administered to healthy male volunteers. In addition to routine safety monitoring, particular attention was directed toward detecting hepatic, neurological, cardiovascular or ocular toxicity. Three of four men who received 3.5 mg/kg of amoscanate developed mild, reversible hepatotoxicity, which could not be unequivocably attributed to the drug. In the second study, of 1 mg/kg amoscanate, there was no statistically significant evidence of hepatotoxicity, although 1 of 12 drug recipients developed transient liver chemistry changes. Despite intensive monitoring, there was no evidence in either study of significant symptomatic complaints, or of neurological, cardiovascular or ocular toxicity. No mutagenic activity attributable to amoscanate was detectable in the urine. These results suggest that this formulation of amoscanate, at 1 mg/kg, is sufficiently well tolerated and safe to justify evaluation for efficacy in patients with schistosomiasis.
单次口服氨硫脲（4-异硫氰酸基-4'-硝基二苯胺），一种实验性抗寄生虫药，在动物体内对感染人类的四种主要血吸虫种类具有高效。设计了两项前瞻性、随机、双盲、安慰剂对照的I期研究，以评估给予健康男性志愿者的2微米颗粒氨硫脲5%水悬浮液的耐受性和安全性。除了常规安全监测外，还特别关注检测肝脏、神经、心血管或眼部毒性。接受3.5毫克/千克氨硫脲的四名男性中有三人出现轻度、可逆的肝毒性，但不能明确归因于该药物。在第二项研究中，接受1毫克/千克氨硫脲的患者中，虽然12名药物接受者中有1人出现短暂的肝功能变化，但没有统计学上显著的肝毒性证据。尽管进行了密集监测，但两项研究中均未发现明显的症状性主诉证据，也未发现神经、心血管或眼部毒性。尿液中未检测到可归因于氨硫脲的诱变活性。这些结果表明，1毫克/千克的这种氨硫脲制剂耐受性良好且安全，足以证明对血吸虫病患者进行疗效评估是合理的。
