盐酸椒苯酮胺对Beagle犬的长期毒性研究  

Study on Long-term Toxicity of Piperphentonmine Hydrochloride in Beagle Dogs

作　　者：李健[1] 李茹冰[1] 张强[1] 陈新[1] 尹雁[1] 朱晋辉 樊鸿浩 邓乐君[2] 付岩霖 李伟达[4] 

机构地区：[1]广州军区广州总医院药剂科,广州510010 [2]南方医科大学,广州510515 [3]广州市众为生物技术有限公司,广州510663 [4]广东药学院中药学院,广州510006

出　　处：《中国药房》2016年第13期1778-1782,共5页China Pharmacy

基　　金：广东省教育部产学研结合项目(No.2012B091100170);广东省科技计划项目(No.2012A080204010);广州市科技计划项目(No.201509010012)

摘　　要：目的:观察连续静脉滴注盐酸椒苯酮胺对Beagle犬产生的长期毒性作用,评价其安全性。方法:取Beagle犬30只,♀♂各半,分成5组,分别为盐酸椒苯酮胺6、12、24、48 mg/kg 4个剂量组和阴性对照组(5%葡萄糖,24 ml/kg),静脉滴注给药,每天1次,连续30 d。检测各组犬的一般生理指标、17项血液生化指标,观察多个部位组织切片的病理变化。结果:24、48 mg/kg盐酸椒苯酮胺组有部分犬在输液完毕后出现一过性平衡或运动失调、四肢无力,一段时间后逐渐恢复;48 mg/kg盐酸椒苯酮胺组犬给药后第15、30天,血浆中丙氨酸转氨酶(ALT)与给药前比较水平升高(P<0.05或P<0.01)。各剂量组犬其他生理指标及其余16项血浆生化指标均未观察到能表明被试药物可致毒性反应的异常改变。病理组织学检查中,24、48 mg/kg盐酸椒苯酮胺组部分犬可见注射部位肿胀,显微镜检查可见注射部位水肿和慢性炎细胞浸润。结论:盐酸椒苯酮胺对Beagle犬的无毒性反应剂量为12 mg/kg,安全剂量范围较大,该结论可作为其临床用药依据。OBJECTIVE：To observe the long-term toxicity of piperphentonamine hydrochloride in Beagle dogs,and to evaluate its safety. METHODS：30 Beagle dogs were evenly composed of male and female and divided into 5 groups,including 4 piperphentonamine hydrochloride groups（6,12,24 and 48 mg/kg）and negative control group（5% glucose,24 ml/kg）. Beagle dogs were given relevant medicines by ivgtt once a day for consecutive 30 days. And general physiological indexes and 17 blood biochemical indicators were detected,and pathological changes were observed in multiple tissues pathological sections. RESULTS：In24 and 48 mg/kg piperphentonamine hydrochloride groups,some dogs suffered from transient balance or movement disorders and weakness,and then recovered after some time. In 48 mg/kg piperphentonamine hydrochloride group,plasma level of ALT increased after 15 and 30 days of treatment,compared to before treatment（P〈0.05 or P〈0.01）. Other physiological indicators and the remaining 16 plasma biochemical indexes of piperphentonamine hydrochloride groups could not explain that there was toxicity reaction. In histopathological examination,some dogs of 24 and 48 mg/kg piperphentonamine hydrochloride groups suffered from injection site swelling,and microscopic examination showed edema and chronic inflammatory cell infiltration. CONCLUSIONS：Piperphentonamine hydrochloride has no toxic reaction to Beagle dogs at the dose of 12 mg/kg. It has some wider safe dose range,and this conclusion can provide evidence for clinical drug use.

关 键 词：盐酸椒苯酮胺 长期毒性 BEAGLE犬 静脉滴注 血液生化指标 

分 类 号：R965[医药卫生—药理学] R972[医药卫生—药学]