肌注硫酸庆大霉素在大肠杆菌感染鸡体内的药动学试验

Pharmacokinetics of Gentamycin in Chicken Infected with Escherichia coli after Intramuscular Administration

为分析硫酸庆大霉素在健康和鸡大肠杆菌感染鸡体内的药物动力学特征,试验通过给健康鸡腹腔注射大肠杆菌O157,以临床症状、病理剖检和微生物检查为指标,成功建立鸡大肠杆菌感染模型。选取健康鸡和患病鸡各8只,分别以20 mg/kg体重单剂量肌内注射硫酸庆大霉素,分别于0.167、0.25、0.5、0.75、1、2、3、4、6、8和12 h时间点采血,采用管碟法测定血浆中庆大霉素的浓度。结果显示:试验所建立的标准曲线相关性好,相关系数均达0.990以上,日内、日间变异系数均小于10%。肌注给药后,硫酸庆大霉素在鸡体内吸收迅速,房室模型分析表明,健康鸡与患病鸡药时数据均符合有二室开放模型,硫酸庆大霉素在健康鸡体内峰浓度(Cmax)为(15.01±3.51)μg/mL,药时曲线下面积(AUC)为(100.79±5.14)μg/mL·h,消除半衰期(t1/2β)为(4.41±1.32)h,达峰时间(Tp)为(1.27±0.50)h。硫酸庆大霉素在患病鸡体内峰浓度(Cmax)为(12.50±2.19)μg/mL,药时曲线下面积(AUC)为(83.38±4.19)μg/mL·h,消除半衰期(t1/2β)为(4.18±1.17)h,达峰时间(Tp)为(0.97±0.05)h。结果表明:硫酸庆大霉素在患病鸡体内的峰浓度和药时曲线下面积低于健康鸡(P<0.05),因此对于已感染大肠杆菌的病鸡可以考虑适当增加给药剂量。

To study the pharmacokinetics properties of Gentamycin and compared in both healthy chicken and chicken infected with Escherichia coli after intramuscular administration.Infection was induced artificially in broiler chickens by an intraperitoneal injection of the suspension of E.coli with indications of clinical signs,necropsy,histopathology and isolation of the pathogen.8 healthy chicken and 8 chicken infected with Escherichia coli were selected randomly.Plasma samples collected at 0.167,0.25,0.5,0.75,1,2,3,4,6,8 and 12 h after administration.The Gentamycin concentration in plasma samples was analyzed using microbiological inhibition method.The drug concentration-time data were analyzed by pharmacokinetic software 3P97.The results revealed that:The correlation of calibration curves were all good,which correlation coeffcients(r)were more than 0.9990.The intra-day and inter-day coefficients of variation were less than 10%.The main pharmacokinetic parameters in heaithy and infected chicken were as follows:The elimination half-life(t1/2β)was(4.41±1.32)h and(4.18±1.17)h.The area under the serum concentration-time curve(AUC)was(100.79±5.14)μg/mL·h and(83.38±4.19)μg/mL·h.The time-point of maximum plasma concentration(Tmax)was(1.27±0.50)h and(0.97±0.05)h and the maximum plasma concentration(C max)were calculated as(15.01±3.51)μg/mL and(12.50±2.19)μg/mL.The conclusion that the maximum plasma concentration(C max)and the area under the serum concentration-time curve(AUC)in infected chicken was significantly lower(P<0.05)than that in healthy chicken.Therefore,the increase in gentamycin dose as a reliable method in infected chicken.