西替利嗪的安全性指标测定

Mensuration of security indices of cetirizine

目的 :分析评价西替利嗪用药的安全性。方法 :按Bliss法测定西替利嗪对组胺致豚鼠休克的ED50 、ED95、ED99和对小鼠的LD50 、LD5、LD1,并计算该药的治疗指数、安全系数、可靠安全系数和安全范围。结果 :西替利嗪口服给药可显著减轻豚鼠静脉注射组胺所致休克反应的严重程度 ,降低休克发生率和死亡率 ,其ED50 、ED95和ED99分别为 0 0 98、0 313和 0 5 0 6mg·kg- 1。小鼠口服给药西替利嗪的LD50 、LD5和LD1分别为 813、386和 2 84mg·kg- 1,而静脉注射西替利嗪的LD50 、LD5和LD1分别为 16 3、12 8和 116mg·kg- 1。经折算成豚鼠的等效剂量后 ,西替利嗪口服给药抗组胺性休克的治疗指数为 5 0 81,安全系数为 75 4 ,可靠安全系数为 344,安全范围为 3430 0 %。结论 :西替利嗪为一种安全有效的抗组胺药。

Aim: To evaluate the security of cetirizine. Methods: The ED 50, ED 95, ED 99 of cetirizine on histamine induced shock and its LD 50, LD 5, LD 1 were determined by Bliss method.The TI, SF, CSF and SM were calculated.Results: The guinea-pigs were effectively decreased reaction extent of histamine induced shock and reduced the rate of shock or death by orally administered cetirizine. The ED 50, ED 95 and ED 99 were 0.098, 0.313 and 0.506 mg·kg -1 respectively in guinea-pigs. In mice the LD 50, LD 5 and LD 1 by orally administered cetirizine were 813, 386 and 284 mg·kg -1 respectively, and the LD 50, LD 5 and LD 1 by vein injected cetirizine were 163, 128 and 116 mg·kg -1 respectively. While histamine induced shock was decreased by orally administered cetirizine, the TI was 5081, SF was 754, CSF was 344, and SM was 34 300%. Conclusion:The cetirizine is a safe and effective antihistamine agent.