Yamaguchi K, Aze Y, Shimizu K, Shichino Y, Oku H, Mori H, Shinomiya K, Ueda H, Suzuki Y, Oida H, Nishibata K, Tanaka M, Yanagizawa Y, Nanba T, Nishiyama K, Yonezawa H, Fujita T
Fukui Institute of Safety Research, ONO Pharmaceutical Co., Ltd., Japan.
J Toxicol Sci. 1998 Jul;23 Suppl 3:457-82. doi: 10.2131/jts.23.supplementiii_457.
A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 18.75, 37.5 or 75 mg/kg. ONO-5046.Na did not affect clinical signs, body weight, food consumption, opthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology at any dose. These results indicate that the NOAEL of ONO-5046.Na in rats is 75 mg/kg/day for both sexes in this study.
对新型中性粒细胞弹性蛋白酶抑制剂N-[2-[4-(2,2-二甲基丙酰氧基)苯磺酰氨基]苯甲酰基]氨基乙酸钠四水合物（ONO-5046.Na）进行了为期6个月的重复剂量毒性研究，并进行了为期1个月的恢复试验，实验动物为Sprague-Dawley（SD）大鼠。雌雄大鼠均静脉注射ONO-5046.Na，日剂量分别为0（溶剂对照）、18.75、37.5或75 mg/kg。在任何剂量下，ONO-5046.Na均未影响临床体征、体重、食物消耗量、眼科检查、尿液分析、血液学、血液化学、器官重量、尸检或组织病理学。这些结果表明，在本研究中，ONO-5046.Na对大鼠的无观察到有害作用水平（NOAEL）为雌雄均75 mg/kg/天。
