国产表阿佛菌素在绵羊体内的药代动力学研究

Study on Pharmacokinetics of Eprinomectin in Sheep Following Intravenous and Subcutaneous Administration

用反相高效液相色谱结合荧光检测法,对试验绵羊经静脉、皮下单剂量注射0.2 mg/kg表阿佛菌素的药代动力学进行了研究.血样提取物通过C18小柱富集、洗脱,甲醇洗提部分经加入1-甲基咪唑和三氟乙酸酐的乙腈液衍生化后进行色谱分析.血药浓度在2.5～200ng/mL范围呈良好线性关系(R=0.996 8),方法平均回收率96.65%±3.84%,血药最低检测限2.5 ng/mL,日内、日间变异系数分别小于10%、12%.2种途径给药后体内药物运转分别符合二室和一室开放模型.主要药代参数如下,静脉注射:消除半衰期(T1/2β)12.66±2.05 h,药时曲线下面积(AUC0～74)1.02±0.30(mg/L)·h,fc=0.13±0.05;皮下注射:吸收半衰期(T1/2ka)4.42±1.04 h,峰浓度(Cmax)0.02±0.01μg/mL,峰时(Tmax)15.36±2.91 h,消除半衰期(t1/2k)26.22±9.04 h,药时曲线下面积(AUC0～122)1.19±0.37(mg/L)·h.上述结果表明,绵羊静脉注射表阿佛菌素后体内药物分布广泛,消除较慢.皮下注射吸收好,消除比静脉注射更为缓慢,体内药物平均滞留时间长.

A RP-HPLC method was used for the determination of eprinomectin concentrations in sheep plasma following i.v. and s.c. administration at a single dose of 0.2 mg/kg. The extract of plasma samples were loaded onto a C_(18) catridge. After solvent exchange,the methanol eluate was derivatized via the addition of 1-methylimidazole and trifluoroacetic anhydride in acetonitrile.Then the fluorescent derivative was analyzed by using fluorescene detector. Eprinomectin in plasma within 2.5~200 ng/mL ranges had a good linear relationship (R=0.996 8) .The average recovery of the method was 99.65%±3.84%.The RSDs of within-day and between-day assays were less than 10%,12% respectively. Drug concentration-time data in plasma were founded to be fitted to a two-compartment open model and one-compartment open model after i.v.and s.c. administration respectively.The main pharmacokinetic parameters demonstrated that eprinomectin was distributed widely and eliminated slowly after i.v. adminstration, After s.c. adminstration it was Absorbed completely and had longer residue time in sheep ,eliminated slower than that of (i.v.) adminstration.