绵羊血浆中多拉菌素的HPLC测定及其药动学研究

Determination of doramectin and its pharmacokinetics in sheep plas ma by HPLC

为利用高效液相色谱法(HPLC)—荧光检测器法测定绵羊血浆中的多拉菌素浓度,并对多拉菌素浇泼剂在绵羊体内的药代动力学进行研究。试验以绵羊6只,按0.5 mg·kg-1·bw-1给药并采血,血浆样品经固相萃取并进行衍生化反应,以反相HPLC测定血浆药物浓度,药代动力学参数用3P97程序进行处理。结果表明,试验条件下血浆中药物添加浓度在0.1～100 ng·mL-1范围内与峰面积呈良好线性关系,检测限为0.1 ng·mL-1,多拉菌素在绵羊体内的动态规律符合二室开放模型。其药物代谢动力学参数分别为:T1/2kα为1.89±0.68 d,T1/2kβ为4.95±0.86 d,Tmax为3.18±0.89 d,Cmax为19.93±0.37 ng·mL-1,AUC为144.7±23.36 ng·d·mL-1。结果显示,多拉菌素浇泼剂在绵羊体内血药浓度较高,吸收分布迅速,体内分布容积较大。研究结果对认识多拉菌素浇泼剂在绵羊体内的药物动力学特征和指导临床用药具有重要意义。

To detect the concentration of doramectin in plasma of sheep by HPLC-FL, the pharmacokinetics of doramectin （DRM） was determined in sheep plasma. Six sheep were treated by inunction with DRM and blood samples were collected at different time points after infection. The blood samples were derivatized after solid phase extraction and analyzed by high performance liquid chromatography （HPLC）. Pharmacokinetic parameters were calculated by using a computerized kinetic program 3P97. The results indicated that the drug concentration-time data of DRM with inunction administration in sheep were accordant with two compartment open model. The main pharmacokinetic parameters were： T1/2kα （1.89±0.68） d, Tl/2kβ （4.95±0.86） d, mmax （3.18±0.89） d, Cmax （19.93±0.37） ng. mL-1, AUC （144.7 ± 23.36） ng-d. mL-1. It demonstrated that DRM was absorbed and distributed rapidly, eliminated slowly, and had a large volume of distribution and a high bioavailability in sheep with inunction administration. Thus, the data should be helpful in understanding the pharmacokinetic characteristics and guiding the use of DRM in sheep in clinic treatment.