大剂量萘哌地尔在家犬体内的药物动力学

Pharmacokinetics of high-dosage naftopidil capsules in dogs

目的 :建立HPLC测定家犬血浆中萘哌地尔浓度的方法 ,研究大剂量萘哌地尔胶囊在家犬体内的药物动力学。方法 :健康家犬 5只 ,单剂量给予萘哌地尔胶囊 2 0 0mg后 ,在不同时间点从后肢静脉取血 ,血浆样品碱化后经乙醚提取 ,以乙腈 :磷酸盐缓冲液 (pH 6 .5 ) (6 0 :40 )为流动相 ,由ODSC18分析柱分离测定 ,紫外 2 30nm为检测波长 ,维拉帕米为内标。血药浓度数据用 3p97药物动力学程度处理。结果 :线性范围为 10～ 12 0 0ng·ml-1;方法回收率为98 83%～ 10 1 5 0 % ;日间RSD≤ 5 5 6 % ,日内RSD≤ 3 30 %。单剂量给予家犬萘哌地尔胶囊 2 0 0mg后 ,血药浓度随时间变化规律符合一室开放模型 ,T1/2Ke为 1 91～ 4 99h ,Tmax为 1 87～ 3 2 1h ,Cmax为 338 79～ 414 0 4ng·ml-1。结论 :本方法简便、回收率高、重现性好 ,用于大剂量萘哌地尔在动物体内的药物动力学研究 ,切实可行。

Objective To establish a high-performance liquid chromatography (HPLC) for the determination of naftopidil in plasma, and make a study of pharmacokinetics of high-dose naftopidil capsules in dogs. Methods Five healthy dogs were treated with naftopidil capsules in an oral single dose of 200 mg. Naftopidil in dog plasma was determined by HPLC. The mobile phase consisted of acetonitrile and 0.05 mol·L -1 phosphate buffer (pH 6.5) (60:40), verapamil was selected as internal standard, and the eluate was monitored at 230 nm. Pharmacokinetics calculations were carried out by practice pharmacoknetics programs (Version 97,3P97). Results The calibration curve of naftopidil was linear within the range of 10～1?200 ng·ml -1 , and the correlation coefficient was 0.9992, the recovery rate of HPLC was (100.23±3.00)%, within day RSD and between day RSD were no more than 5.56% and 3.30% respectively. The plasma drug concentration-time course in dogs conformed to the one-compartment model. T 1/2Ke value was (1.91～4.99) h, T max was (1.87～3.21)h, C max was (338.79～414.04) ng·ml -1 . Conclusion HPLC is accurate and reliable, and can be used for studying the pharmacokinetics of high-dose naftopidil capsules in dogs.