多拉菌素在犬体内药代动力学研究

 采用RP-HPLC法荧光监测器测定单剂量皮下注射多拉菌素［300μg/（kg BW）］）后，犬体内不同时间点的血浆药物浓度。血浆药物浓度-时间数据采用3P97药动软件分析。结果表明，本试验条件下血浆中药物添加浓度在0.1～100 ng/mL范围内与峰面积呈良好线性关系，检测限为0.5 ng/mL。不同浓度水平的日内日间变异系数分别小于3%和4%，各浓度的平均回收率均大于90%。给药后血药浓度－时间数据符合一级吸收一室开放模型，主要药物动力学参数为：t_1/2ka为（0.58±0.13）d，t_1/2β为（4.78±0.31）d，T_max为（2.00±0.29）d，C_max为（20.29±2.04）ng/mL，AUC为（187.43±24.99）（ng·d）/mL。提示多拉菌素在犬体内血药浓度维持的时间长，消除缓慢，且根据其半衰期判断，多拉菌素属于慢性消除药物。

Pharmacokinetics of Doramectin in Dogs

The pharmacokinetics studies of doramectin in dog following single subcutaneous administration at a dose of 300 μg/kg were conducted in this paper. The concentration of doramectin was detected with reversed phase high performance liquid chromatorgraphic method with fluorescence detector.The concentration-time data were calculated with 3P97.Under this experiment condition,Lineary was expressed by correlation between chromatographic peak areas and concentration of standards at a wide concentration range of 0.1～100 ng/mL, the standard calibration curve was linear in this range and the detectability was 0.5 ng/mL.Three concentradtion levels of doramectin were analysed,the intra-day and the inter-day coefficient of variance was respectively less than 3% and 4%,the average recovery was respectively more than 90%.The procession of doramectin after single subcutaneous administration was fit the one-compartment open model with first-order absorption.The main pharmacokinetic parameters of doramectin in dog were as follows: t_1/2ka （0.58±0.13）d, t_1/2β（4.78±0.31）d,T_max（2.00±0.29）d,C_max（20.29±2.04）ng/mL,AUC（187.43±24.99）（ng·d）/mL.The results showed that doramectin has a long persistence in the plasma concentrations and eliminated slowly in dog.Based on the elimination half-life of doramectin in dog,it can be considered as a drug with slowly elimination rate.