国产湿痛喜康的毒性研究

给小鼠iv和ig国产湿痛喜康,LD_(50)分别为135±10.27和320±96mg/kg。给佐剂性关节炎大鼠ig湿痛喜康28d,体重增加,血清AKP、SGPT和BUH无明显改变。病解无明显形态学变化。给3条狗ig湿痛喜康16mg/kg, 每天1次,连用5d,两条中毒死亡,1条存活。另3条狗ig湿痛喜康16mg/kg,隔日1次,自首剂给药后10～20d达到稳态中毒血药浓度(分别为73.9,44.9,72.5μg/ml)。于给药后17～25d死亡。出凝血时间延长约2～3倍,血浆BUN值升高。病检除1条狗可见间质性肾炎和肝细胞局灶性坏死外,其余未见明显特征性改变,给大鼠ig湿痛喜康(5、10、20和40mg/kg),对消化道有损伤作用。UD_(50)为14.75mg/kg(95％可信区间为19.4～19.93mg/kg),与血药浓度呈平行关系。

STUDIES ON THE TOXICITY OF SUDOXICAM

The acute iv and ig LD50 of sudoxicam synthesized by Shanyan Ph-armaceutic College was calculated to be 135±10. 7 and 320 ± 96 mg/kg in mice. In polyarthritic rats, Sud at 2 and 4 mg/kg/d for 28 days did not induce changes in serum AKP, SGPT, BUN the morphal-ogic characteristics of the gastrointestinal tract, liver and kidney. In 3 dogs orally given Sud 16 mg/kg/d for 5 consecutive days, 2/3 died at days 10 to 13. In other 3 dogs given Sud 16 mg/kg/d every other day, plasma concentrations of Sud were determined by ultra violet spectrophotometry. It was found that on the days 10 to 20 , the concentration time curves had attained a intoxicant steady state with plasma sudoxicam concentrations as high as 44. 9 ± 73. 9μg/ml ,and all of them died after 17~25 days. Their bleeding time and coagu- lation time were prolonged to 2 or 3 times of the control and serum BUN was increased. In one dog autopsy revealed the interstitial inflammation of the kidney and small local necrosis of the live, but not in other dogs.Gastric ulceration in rats can be produced by the oral administration of verious doses of Sud. The UD50 of Sud was 15.47mg/kg. It was found that the gastric ulceration in rats is related to the plasma levels