Onodera C, Hayashi T, Makita I, Hashi T, Takeda K, Ozeki F, Shimazu H
J Toxicol Sci. 1979 Aug;4(3):229-53. doi: 10.2131/jts.4.229.
Male and female dogs, aged 17--21 months, were administered orall M 73101 (0, 60, 120 and 240 mg/kg/day), a new analgesic and antiinflammatory drug, for 27 weeks, and following recovery test was carried out for 5 weeks. Dead animals were not found throughout the experimental period. Body weight gain, and food and water consumption were not affected due to M 73101 administration. Except for a slight increase of vomitting in the highest dose, there were no abnormal symptoms. Biochemical examination showed the slight increase in serum alkaline phosphatase activity and free cholesterol level. Pathological examination revealed a dose-dependent increase of liver weight and hypertrophy of hepatocytes due to proliferation of smooth endoplasmic reticulum. In addition, mitochondria became irregularly large in the highest dose. There were no abnormal findings in the gastro-intestinal tracts except for an erosion of gastric mucosa, which was noted in a female dog treated 240 mg/kg/day of M 73101. From these results, it was suggested that the maximum non-toxic dose was 60 mg/kg/day or less, and the greatest safety dose was 120 mg/kg/day in beagle dogs.
对年龄在17至21个月的雄性和雌性犬口服给予新型镇痛抗炎药物M 73101（0、60、120和240毫克/千克/天），持续27周，并进行5周的恢复期试验。在整个实验期间未发现死亡动物。给予M 73101未影响体重增加、食物和水的消耗。除最高剂量组出现轻微呕吐增加外，未出现异常症状。生化检查显示血清碱性磷酸酶活性和游离胆固醇水平略有升高。病理检查发现肝脏重量呈剂量依赖性增加，肝细胞肥大，原因是滑面内质网增生。此外，最高剂量组线粒体变得不规则增大。除一只接受240毫克/千克/天M 73101治疗的雌性犬出现胃黏膜糜烂外，胃肠道未发现异常。从这些结果来看，在比格犬中，最大无毒剂量为60毫克/千克/天或更低，最大安全剂量为120毫克/千克/天。
