摘要
目的研究蒿甲醚自微乳化给药系统提高蒿甲醚在大鼠体内的口服相对生物利用度,并建立快速、简单测定大鼠血浆中蒿甲醚浓度的HPLC-MS/MS方法。方法 12只大鼠按照随机数字表法分为2组,分别灌胃给药给予自制的蒿甲醚混悬液和蒿甲醚自微乳化给药系统,测定蒿甲醚的血浆药物浓度,评价蒿甲醚自微乳化给药系统给药后的相对生物利用度。结果本方法大鼠血浆中蒿甲醚浓度的线性范围为5.035-402.8 ng/mL（r=0.999 7）;日内及日间精密度RSD均小于15%。单剂量口服灌胃给药给予蒿甲醚混悬液120 mg/kg和蒿甲醚自微乳化给药系统20 mg/kg后,血浆中蒿甲醚的Cmax分别为（96.33±37.34）、（183.59±48.32）ng/mL;AUC0→t分别为（304.86±75.27）、（842.18±151.55）ng·h/mL,AUC0→∞分别为（322.66±79.32）、（979.90±172.71）ng·h/mL。以AUC0→t和AUC0→∞计算,蒿甲醚自微乳化给药系统的相对生物利用度分别为1 658%和1 822%。结论自微乳化给药系统可以增加蒿甲醚口服吸收,提高其生物利用度。
Objective To determine the effects of self-microemulsifying drug delivery system（SMEDDS） on the relative bioavailability of artemether（ARM） in rats after oral administration,and to set up an HPLC-MS /MS method to determine the concentration of ARM in rat plasma.Methods Twelve rats were randomly divided into two groups,which were separately treated with a single dose of 120 mg /kg ARM suspension and 20 mg /kg ARM SMEDDS.The concentration of ARM in rat plasma was tested,and the pharmacokinetic parameters and the relative bioavailability of ARM SMEDDS were calculated.Results The linear range of ARM in rat plasma was 5.035 to 402.8 ng /mL（r = 0.999 7）.The intra-day and inter-day RSDs were less than 15%.After a single dose of 120 mg /kg ARM suspension or 20 mg /kg ARM SMEDDS,pharmacokinetic parameters were：Cmax96.33 ± 37.34 and 183.59 ± 48.32 ng /mL,respectively,AUC0→t 304.86 ± 75.27 and 842.18 ± 151.55 ng·h /mL,respectively,and AUC0→∞322.66 ± 79.32 and 979.90 ± 172.71 ng ·h /mL,respectively.The relative bioavailability of ARM SMEDDS was 1 658% and 1 822% calculated with AUC0→t and AUC0→∞,respectively.Conclusion SMEDDS significantly improves the oral bioavailability of ARM and may be a promising carrier for ARM.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2014年第14期1481-1485,共5页
Journal of Third Military Medical University
基金
重庆市卫生局医学科研计划项目(2012-2-261)~~
关键词
蒿甲醚
自微乳化给药系统
相对生物利用度
artemether
self-microemulsifying drug delivery system
relative bioavailability
