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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 study the pharmacokinetics of doxorubicin-heparin mesoporous silica anticancer drug system (AMS-HP) in rats. Methods Six Sprague-Dawley rats were injected sublingual AMS-HP into the sublingual vein at a dose of 8 mg · kg -1 before and at 0,0.08,0.17,0.5,1,3,6,12, The tail vein blood was collected at 24, 36, 48, 60 and 72 h, the plasma concentration of doxorubicin in AMS-HP was determined by HPLC, and the main pharmacokinetic parameters were calculated by DAS 2.0. Results The main pharmacokinetic parameters C_max, t_ (1/2), t_ (max), V / F, CL / F, AUC0-t and AUC0-∞ of adriamycin in AMS- 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 and 3838.51 ± 817.60 ng · m L -1 · h, respectively. Conclusion In this study, a HPLC method for the determination of AMS-HP in blood serum was established and validated by methodology. The half-life of doxorubicin in AMS-HP was prolonged and sustained release in vivo was achieved.