黄芪注射液多剂量给药对雷替曲塞在大鼠体内药动学行为影响  

Pharmacokinetics behavior of raltitrexed in rats after repeatedly injected with Huangqi injection

作　　者：邢蓉[1] 屈彪[2] 宋佳伟[3] 周恺[2] 廖巧[3] 

机构地区：[1]蚌埠医学院第一附属医院,安徽蚌埠233000 [2]安徽中医药大学药学院,安徽合肥230000 [3]蚌埠医学院药学系,安徽蚌埠233000

出　　处：《中国中药杂志》2014年第11期2140-2143,共4页China Journal of Chinese Materia Medica

基　　金：安徽省自然科学基金项目(1408085MH206)

摘　　要：该研究揭示了黄芪注射液多次给药对雷替曲塞大鼠体内药动学行为影响。12只SD大鼠分为多剂量组和对照组,多剂量组每天早晨8点尾静脉注射黄芪注射液,连续给药7 d。第8天早注射黄芪注射5 min后,注射雷替曲塞溶液;对照组前7天不做处理,第8天与多剂量组同时注射雷替曲塞溶液。分别于大鼠雷替曲塞给药后不同时间点采血,处理后经HPLC进样分析,并计算药动学参数。从大鼠血浆药时曲线中可以看出,多剂量组与对照组相比,各时间点浓度均较低,AUC和t1/2均值分别由56 080μg·min·L-1和15.07 min减小到35 834μg·min·L-1和8.95 min,CL则由0.51 mL·h-1提高至0.83mL·h-1,推测黄芪注射液多次给药后可影响大鼠对雷替曲塞的糖代谢和肾排泄功能,进而使其药动学行为发生变化。In this study, the variation of pharmacokinetics behavior of raltitrexed（RTX） in rats after repeatedly injected with Huangqi injection was investigated. Twelve SD rats were divided into two groups： the multidose group and the RTX group. Rats in multidose group were iv. injected with Huangqi injection（dose of 1.575 mL·kg^-1） everyday at 8 am for a week, and had free accesses for food and water. The rats were fasted for food but not water since 8 h before the eighth day. At the eighth morning, firstly, rats were injected with Huangqi injection（dose of 1.575 mL·kg^-1）, and 5 min later, were injected with RTX（dose of 0.467 mg·kg^-1）; rats in RTX group were not disposed in the previous seven days, also had free accesses for food and water, and were iv. injected with raltitrexed at the same time as Multidose group at the eighth day morning. Rat plasma was collected at different time and processed with methanol to precipitate the protein before HPLC assays. The pharmacokinetics parameters for two groups were calculated by software 3P97. Through the observation of drug concerntration in plasma and time curve, we found that at almost every time point the concerntration of RTX in plasma in multidose group was lower than the RTX group. When comparing the pharmacokinetics parameters between the multidose group and the RTX group, the average of AUC0-t and half-life（t1/2） of multidose group were decreased from 56 080 μg·min·L^-1and 15.07 min to 35 834 μg·min·L^-1and 8.95 min, respectively, while the clearance（CL） was increased from 0.51 to 0.83 mL·h^-1. Therefore, it could be deduced that repeatedly injected with AR injection may influence the renal excretion and glycometabolism of RTX, thus change pharmacokinetics behavior of raltitrexed in rats plasma. This result may give us a hint to prudantly manage the drug combination of RTX and Huangqi injection.

关 键 词：雷替曲塞 黄芪注射液 相互作用 药动学 

分 类 号：R285.6[医药卫生—中药学]