阿霉素-肝素介孔硅抗癌药物系统在大鼠体内的药代动力学

Pharmacokinetic processes of adriamycin-heparinized mesoporous silica anticancer drug delivery system in rats

目的研究阿霉素-肝素介孔硅抗癌药物系统(AMS-HP)在大鼠体内的药代动力学过程。方法6只SD大鼠舌下静脉注射AMS-HP,剂量8 mg·kg^(-1),分别在给药前和给药后0,0.08,0.17,0.5,1,3,6,12,24,36,48,60,72 h采集尾静脉血,用HPLC法测定AMS-HP中阿霉素的血药浓度,用DAS 2.0计算主要的药代动力学参数。结果 AMS-HP中阿霉素的主要药代动力学参数C_(max)、t_(1/2)、t_(max)、V/F、CL/F、AUC0-t、AUC0-∞分别为(5.71±0.46)L·h^(-1)·kg^(-1),(15.81±2.01)h,(3.00±0.00)h,(140.12±17.87)L·kg^(-1),(118.74±18.04)ng·m L^(-1),(3599.96±881.99)ng·m L^(-1)·h,(3838.51±817.60)ng·m L^(-1)·h。结论本研究建立了AMS-HP血药浓度检测的HPLC法并进行了方法学验证,AMS-HP中阿霉素的半衰期延长,在体内具有缓释效果。

Objective To investigate tile pharmacokinetic processes of adriamycin- heparinized mesoporous silica anticancer drug delivery sys- tem （AMS- HP） in rats. Methods Six male Sprague -Dawley rats were used. AMS - HP was administered intravenously via a sublingual vein with a dose of 8 mg·kg-1. Blood was sampled from the tail before treatment and 0, 0. 08, 0. 17, 0. 5, 1,3, 6, 12, 24, 36, 48, 60, 72 h after given drags. The plasma concentration of adriamycin in AMS - HP was determined by HPLC. The pharmacokinetic parameters were deter- mined by DAS 2.0 software. Results The main pharmacokinetic param- eters of adriamycin in AMS - HP were as follows： C_（max）、t_（1/2）、t_（max）、V/F、CL/F、AUC0-t、AUC0-∞（5.71±0.46）L·h-（-1）·kg-（-1）,（15.81±2.01）h,（3.00±0.00）h,（140.12±17.87）L·kg-（-1）,（118.74±18.04）ng·m L-（-1）,（3599.96±881.99）ng·m L-（-1）·h,（3838.51±817.60）ng·m L-（-1）·h. respectively. Conclusion The HPLC method of plasma concentration of adriamycin in AMS - HP is specific and has good accuracy, precision and high sensitivity. Adriamy- cin in AMS- HP has a long half- life and a slow release effect in vivo.