盐酸青藤碱控释微丸犬体内药物动力学研究.doc

通讯作者：张淑秋，教授，博士，山西医科大学药学院，0351-4690140，shuqiu.zhang@ 该项目由山西省归国人员基金资助，项目编号2005029 盐酸青藤碱控释微丸犬体内药物动力学研究 张丽锋，白克华，张淑秋*(山西医科大学药学院临床药学教研室 太原030001) 摘要 目的：测定盐酸青藤碱控释微丸犬体内药物动力学参数，计算相对生物利用度。方法：采用反相高效液相色谱法，流动相为甲醇-已腈-0.05 mol·L-1磷酸二氢铵溶液（50∶12∶190 v/v/v），柱温为30 ℃，流速为0.7 mL·min-1；检测波长为264 nm；结果：盐酸青藤碱在50~4000 ng·mL-1范围内线性关系良好，线性方程为R = 3.6×10-4C＋0.06，r = 0.9964，方法的精密度和回收率均符合中国药典的规定。受试制剂和参比制剂的主要药物动力学参数分别为：t1/2：19.9±4.3 h、17.8±2.1 h；Cmax：638±128 ng·mL-1、1738±396 ng·mL-1；Tmax：6.2±1.1 h、7±1 h；AUC0~t：20739.77±4100 h·ng·mL-1、14906.54 ±9219 h·ng·mL-1，相对生物利用度为90.1±10.4 %。结论： 关键词：盐酸青藤碱；微丸；高效液相色谱；药物动力学 Pharmacokinetics of sinomenine hydrochloride controlled-release pellets in dogs ZHANG Li-feng，BAI Ke-hua，ZHANG Shu-qiu（Dept. of Clinical Pharmacy, Faculty of Pharmacy College, Shanxi Medical University, Taiyuan 030001 China） Abstract Objective: To determine pharmacokinetic parameters of sinomenine hydrochloride controlled-release pellets in dogs and calculate the relative bioavailability. Methods：To use a high performance liquid chromatography (HPLC) method with the mobile phase consisted of methanol, acetonitrile and 0.05 mol·L-1 ammonium dihydrogen phosphate solution(50∶12∶190 v/v/v), the column temperature was 30 ℃, the flow rate of mobile phase was 0.7 mL·min-1 and the wavelength of detector was set at 264 nm. Results：The linear range of sinomenine hydrochloride was 50~4000 ng·mL-1, R = 3.6×10-4C＋0.06，r = 0.996. The precision and recovery were fit for China Pharmacopeia. The pharmacokinetic parameters were t1/2（19.9±4.3）and（17.8±2.1）h, Cmax(638±128)and（1738±396） ng·mL-1,Tmax（6.2±1.1） and（7±1）h, AUC0~t（20739.77±4100） and（14906.54±9219） h·ng·mL-1 for test and reference preparations, respectively. The relative bioavailability was 90.1±10.4 %。Conclusion：The concentration-time curve of sinomenine hydrochloride controlled-release pellets in dogs was flatter and the duration was longer. The present studies achieved our prospective aims. Key words：sinomenine hydrochloride; pellets; HPLC; pharmacok