新型三嗪类药物沙咪珠利在感染柔嫩艾美耳球虫鸡体内不同浓度下药物动力学

Pharmacokinetics of a New Triazine Drug Ethanamizuril in Chickens Infected with Eimeria tenella

沙咪珠利(EZL)是中国农业科学院上海兽医研究所自主研发的一种新型三嗪类抗球虫药物。本研究通过建立鸡球虫感染模型,进行感染鸡灌胃给药沙咪珠利4 mg/kg.bw与8 mg/kg.bw两种剂量后的药动学研究,采用高效液相色谱法测定鸡血浆中沙咪珠利药物浓度,使用DAS3.0非房室模型拟合分析药动学参数。选取健康鸡160只于15日龄时每只鸡感染柔嫩艾美尔球虫孢子化卵囊80000,感染后鸡只分为两组,每组分别选取75只感染模型于第5 d分别灌胃给药沙咪珠利4 mg/kg.bw与8 mg/kg.bw。感染鸡给药前后分别于0、0.5、1、2、3、4、6、8、12、24、36、48、60、72 h,每个时间点取5只鸡心脏采血,血浆样品-20℃保存待测。结果表明,感染鸡灌胃给药4 mg/kg.bw与8 mg/kg.bw后其最高血药浓度(C_(max))分别为4.28±1.56μg/mL与11.82±0.59μg/mL;达峰时间(T_(max))分别为5.2±3.83 h与8.8±1.80 h;AUC_(0-t)分别96.90±16.31 mg/L*h与351.61±36.06 mg/L*h;消除半衰期(t_(1/2z))分别为13.83±5.13与15.07±7.47 h。

Ethanamizuril(EZL)is a new triazine anticoccidial drug independently developed by Shanghai Veterinary Research Institute,Chinese Academy of Agricultural Sciences.In this study,chickens were administered via gavage with EZL at 4 mg/kg.bw and 8 mg/kg.bw and its pharmacokinetics in these infection models were studied using high performance liquid chromatography method and DAS3.0 software.Total 160 healthy chickens were used in the study.Each chicken was infected with 80000 sporulated oocysts of Eimeria tenella at 15 days of age.After infection,chickens were divided into two groups with 75 each.On the 5th day post infection,chickens were administered with EZL at dosage of 4 mg/kg.bw and 8 mg/kg.bw,respectively.Blood samples were taken from 5 chicken hearts at time point 0,0.5,1,2,3,4,6,8,12,24,36,48,60 and 72 h post infection.These samples were centrifugated and stored at-20℃till use.The EZL measurements showed that the highest plasma concentrations(C_(max)),peak times(T_(max)),area under drug time curve(AUC_(0-t))and elimination half-life (t_(1/2z)) were 4.28±1.56 μg/mL, 5.2±3.83h, 96.90±16.31 mg/L*h and 13.83±5.13 for 4 mg/kg.bw, and 11.82±0.59 μg/ mL, 8.8±1.80 h, 351.61±36.06 mg/L*h and 15.07±7.47 h for 8 mg/kg.bw, respectively.