多拉菌素在猪体内的药代动力学

Pharmacokinetics of Doramectin in Pigs

对多拉菌素在猪体内进行为期45d的药代动力学研究。长白×杜洛克杂交猪10头,临床健康,驱净寄生虫,体重36～50kg,以300μg/kg体重剂量分别通过静脉和肌肉注射给药。动物给药后在不同时间内分点经颈静脉采血。血浆样品用乙腈沉淀处理,上清液过C18富集柱,用甲醇提取多拉菌素并进行衍生化反应,以反向HPLC测定猪血清中的药物浓度。药代动力学参数用计算机程序MCPKP进行处理。结果表明,动物经静脉和肌肉注射给药后,血浆药物浓度分别可测至30d和25d,2种途径的药物浓度时间曲线均符合二室开放模型。主要药代动力学参数为:静脉注射T1/2α(1.092±0.66)d,T1/2β(6.11±2.73)d,AUC(274.19±119.89)μg/(L·d);肌肉注射T1/2α(0.056±0.022)d,T1/2β(3.20±1.34)d,AUC(223.51±65.20)μg/(L·d),CMAX(28.99±10.69)μg/L,Tp(1.24±0.87)d。多拉菌素肌肉注射的生物利用度为81.5%。结果显示多拉菌素在猪体内具有吸收分布较迅速、体内分布容积大、消除缓慢和生物利用度相对较高的特点,提示多拉菌素在猪体内作用的长效性主要由该化合物的自身特性所决定,而与给药途径和使用的溶剂关系不大,研究结果对指导临床正确用药具有重要意义。

The plasma pharmacokinetics of doramectin (DRM) after intravenous (i.v.) and intramuscular (i.m.) administration at a single dose of 300 μg/kg b.w. were determinined over a 45-day period in pigs. Ten crossbreed pigs, clinical healthy, parasite free, weighing 36~50 kg were selected for study. Pigs were located into 2 groups of 5 animals and were treated with 300 μg/kg b.w. DRM with i.v. and i.m. injection, respectively. Blood samples were collected from jugular vein at different time points in 45 days after drug administration. The separated plasma were derivatized after solid phase extraction and analysed by high performance liquid chromatography (HPLC). Pharmacokinetics parameters were calculated by a computerized kinetic program MCPKP. The mean plasma concentration of DRM after i.v. and i.m. administration were detected until 30 and 25 days, respectively. Both drug concentration-time data of DRM with i.v. and i.m. administration accorded with two compartment open model in pig. The main pharmacokinetics parameters were: T_(1/2α)(1.092±0.66) d,T_(1/2β)(6.11±2.73) d, AUC (274.19±119.89) μg ·L^(-1)·d^(-1) for i.v., and T_(1/2α) (0.056±0.022) d,T_(1/2β)(3.20±1.34) d,AUC (223.51±65.20) μg·L^(-1)·d^(-1), C_(MAX) (28.99±10.69) μg/L,Tp (1.24±0.87) d for i.m.,respectively. The general bioavailability of DRM with i.m. injection was 81.5%. The results indicated that DRM was rapidly absorbed and distributed, slowly eliminated and possessed large volume of distribution, high bioavailability in pig with i.v. and i.m. administration. It suggested that the long activity of DRM in pig was likely to resulted from the intrinsic characteristic of DRM rather than different routes of drug administration or the kind of solvent used. Therefore, the results are helpful for understanding the pharmacokinetics characteristics and correct using of DRM in pig in clinic.