10%磷酸替米考星可溶性粉的安全药理学研究

Study of safety pharmacology on 10% tilmicosin phosphate soluble powder

探讨了10%磷酸替米考星可溶性粉对家犬心血管系统与呼吸系统、小鼠神经系统及大鼠消化系统和泌尿系统的影响。结果显示,10%磷酸替米考星可溶性粉40、20和10 mg/kg剂量组和阴性对照组（蒸馏水）经十二指肠给药后180 min内,受试麻醉犬各剂量组各时间点血压、呼吸频率、呼吸幅度及各项心电图指标给药前后自身对照,无显著性统计学意义（P〉0.05）。对小鼠神经系统的试验结果显示,该药240、120和60 mg/kg剂量组和阴性对照组（蒸馏水）灌胃给药后对小鼠耳壳血管及尾色泽无明显影响,各剂量组小鼠活动正常;10%磷酸替米考星可溶性粉各剂量组与阈下剂量的戊巴比妥钠无协同作用,对小鼠自发活动没有明显影响。该药120、60和30 mg/kg剂量组和阴性对照组（蒸馏水）灌胃给药后,除高剂量组大鼠血清总蛋白、白蛋白质量浓度显著升高,中剂量组尿素氮浓度显著升高外（其值仍在正常范围内）,3个用药组对大鼠胆汁分泌、肠推进、胃液分泌、尿常规、泌尿系统相关血清生化指标均无明显影响。研究结果表明,10%磷酸替米考星可溶性粉在受试剂量范围内对家犬心血管系统和呼吸系统、小鼠机能协调和大鼠消化系统与泌尿系统均无显著影响。

The effects of 10% tilmicosin phosphate soluble powder on the cardiovascular system and respiratory system of domestic dogs,mouse nervous system,and rat digestive and urinary system were investigated.The results showed that after drug administration through the duodenum,in the period of180 min,blood pressure,breathing rate,respiratory amplitude and electrocardiogram in the tested dogs were not influenced by 40 mg/kg,20 mg/kg and 10 mg/kg of 10% tilmicosin phosphate soluble powder and distilled water（negative control）,which illustrated the tested drug was safe for cardiovascular system and respiratory system of dogs.The experimental results of tested drug on mouse nervous system showed that mouse auricular and tail color were not affected by the gavage of 240 mg/kg,120 mg/kg and 60 mg/kg of 10% tilmicosin phosphate soluble powder,the mouse behavior and functional coordination was also not impacted obviously,and all groups of tested drug did not show synergistic effect with pentobarbi-tal sodium at the subthreshold dose,and not influence the autonomic activity of mouse（P〉0.05）.The results on rat digestive and urinary systems showed that 120 mg/kg,60 mg/kg and 30 mg/kg of the tested drug would not change the normal function of bile secretion,intestinal propulsion,gastric secretion,urine routine,blood biochemical index related to urinary system,except for the increase（within the normal range） of serum total protein and albumin mass concentration in high dose group and urea nitrogen concentration in middle dose group.In conclusion,tilmicosin phosphate showed a good characteristics of safety pharmacology.