小鼠、大鼠和比格犬乐福昔布的急性毒性研究

Acute toxicity of lefucoxib in rats, mice and Beagles

目的了解单次给药后动物所产生的毒性反应,计算LD50剂量或最大给药剂量,为安全用药提供参考。方法NIH小鼠空腹灌乐福昔布1次,剂量为5.0g/kg,连续观察1周;大鼠剂量为2g/kg。比格犬单次灌胃乐福昔布近似致死剂量试验。结果NIH小鼠服用受试药后1周内体重变化与对照组比较无统计学差异,最大耐受剂量(MTD)>5.0g/kg。大鼠给药组进食量及体重与对照组比较无明显差异。比格犬食欲、活动、体温正常,心率和心电图与给药前比较无统计学差异,给药后7d处死动物,心、肝、肾、肺、脾及消化道未见淤血、出血及感染灶等病变。结论乐福昔布属低毒药,测不出比格犬近似致死剂量,最高非致死剂量大于5.0g/kg。

Objective To observe the toxic reaction in animals after a single drug was given and to calculate the LD50 or the maximum dose. Methods NIH mice were given lefucoxib by garage at the dose of 5.0g/kg, once a week for 10 weeks, and the largest volume was 0.8mL. Acute toxicity in rats was detected after a single fixed-dose of oral lefucoxib （2 000mg/kg）. Beagles received an approximate lethal dose of lefucoxib in accordance with ＂the Guiding Principles of Chemical and Therapeutic Biological Products＂. Results No statistical change was found in body weight between NIH mice and controls one week after treatment. The maximum tolerable dose was over 5.0g/kg. No statistical difference was observed in the food intake and body weight of rats between treatment and control groups. The appetite, activity and body temperature of beagles were normal with no obvious change in heart rate and electrocardiogram. No congestion, bleeding and infection occurred in the heart, liver, kidney, lung, spleen and digestive tract of beagles. Conclusion Lefucoxib has low toxicity and the approximate lethal dose cannot be determined in beagles. The highest nonlethal dose is over 5.0g/kg.