Yanagi H, Yamaguchi K, Shimizu K, Shichino Y, Nishiyama K, Mori H, Shinomiya K, Ueda H, Suzuki Y, Yonezawa H, Fujita T
Fukui Institute for Safety Research, ONO Pharmaceutical Co., Ltd., Japan.
J Toxicol Sci. 1998 Jul;23 Suppl 3:409-13. doi: 10.2131/jts.23.supplementiii_409.
Single-dose toxicity studies of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, were conducted in Sprague-Dawley (SD) rats and beagle dogs. The rats of both sexes were administered ONO-5046.Na intravenously at a single dose of 150, 300 or 450 mg/kg. The male dogs were also given ONO-5046.Na at a single dose of 75 or 150 mg/kg. In the rat study, hypoactivity, bradypnea and paleness of limbs and pinna were observed at doses of 300 mg/kg and above. In particular, one of six female rats in the 450 mg/kg group showed clonic convulsion and died. In surviving animals, those signs disappeared within 3 hr after administration. No effect on body weight gain was seen in either group. Necropsy findings showed a slight foamy fluid in the bronchus, hemorrhage at the right knee joint muscle, tendon and lung in a dead animal. In the dog study, no effects on clinical signs, body weight, food consumption and blood biochemistry were seen in any animals of the 75 and 150 mg/kg groups. It is concluded that the approximate lethal doses are 450 mg/kg in rats and 150 mg/kg and above in dogs.
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)苯基磺酰氨基]苯甲酰]氨基乙酸钠四水合物（ONO-5046.Na）的单剂量毒性研究在Sprague-Dawley（SD）大鼠和比格犬中进行。对雌雄大鼠静脉注射单剂量150、300或450 mg/kg的ONO-5046.Na。对雄性犬也给予单剂量75或150 mg/kg的ONO-5046.Na。在大鼠研究中，在300 mg/kg及以上剂量时观察到活动减退、呼吸徐缓和四肢及耳廓苍白。特别是，450 mg/kg组的6只雌性大鼠中有1只出现阵挛性惊厥并死亡。在存活的动物中，这些体征在给药后3小时内消失。两组均未观察到对体重增加有影响。尸检结果显示，一只死亡动物的支气管中有少量泡沫状液体，右膝关节肌肉、肌腱和肺部有出血。在犬类研究中，75和150 mg/kg组的任何动物在临床体征、体重、食物消耗和血液生化方面均未观察到影响。结论是，大鼠的近似致死剂量为450 mg/kg，犬的近似致死剂量为150 mg/kg及以上。
