摘要
目的:探究羟基喜树碱(HCPT)磁性脂质体在大鼠体内药代动力学特征,为该药物的制剂开发提供参考。方法:建立微透析样品中开环HCPT(C-HCPT),闭环HCPT(L-HCPT)的HPLC,SD大鼠尾静脉注射HCPT磁性脂质体和HCPT注射液,腹腔注射HCPT注射液(剂量以HCPT计均为10 mg·kg-1),于给药后采用微透析技术定时采样。微透析样品经各样本自身体内回收率校正,利用DAS 2.1.1软件计算相关药物动力学参数。结果:HCPT磁性脂质体尾静脉给药组,HCPT注射液尾静脉给药组和HCPT注射液腹腔给药组的药峰浓度(Cmax)分别为(2.789±0.158),(4.537±0.092),(0.340±0.066)mg·L-1,达峰时间(tmax)分别为(24±0),(6±0.127),(24±0.127)min,平均滞留时间(MRT0-∞)分别为(72.255±4.668),(20.325±4.288),(112.630±29.969)min,药时曲线下面积(AUC0-∞)分别为(216.870±3.271),(150.668±7.306),(34.883±10.245)mg·L-1·min;与HCPT注射液尾静脉给药组相比,HCPT磁性脂质体尾静脉给药组的tmax,MRT0-∞较大,差异有统计学意义;与HCPT注射液腹腔给药组相比,HCPT磁性脂质体尾静脉给药组的Cmax,AUC0-∞较大,差异有统计学意义。结论:HCPT磁性脂质体尾静脉注射能显著提高药物血药浓度、生物利用度及其在体内的滞留时间;且脂质体可保护HCPT活性必需基团内酯环不被破坏,从而保证HCPT的抗肿瘤活性。
Objective： To study on the pharmacokinetics of hydroxycamptothecin（ HCPT）magentolipsomes in rats. Method： The detection method for open-loop HCPT（ C-HCPT） and closed-loop HCPT（ L-HCPT） in microdialysis samples were established by HPLC. The microdialysis samples were collected after they were treated with HCPT magentolipsomes（ intravenous injection）,HCPT injection（ intravenous injection）and HCPT injection（ intraperitoneal injection） at a concentration of 10 mg·kg^（-1）for HCPT. The microdialysis samples were corrected with in vivo recoveries,the pharmacokinetic parameters were calculated by DAS 2. 1. 1software. Result： The pharmacokinetic parameters of HCPT magentolipsomes（ intravenous injection）, HCPT injection（ intravenous injection） and HCPT injection（ intraperitoneal injection） were calculated as follows： Cmax of（ 2. 789 ± 0. 158）,（ 4. 537 ± 0. 092）,（ 0. 340 ± 0. 066） mg·L-1,tmaxof（ 24 ± 0）,（ 6 ± 0. 127）,（ 24 ±0. 127） min,MRT0-∞of（ 72. 255 ± 4. 668）,（ 20. 325 ± 4. 288）,（ 112. 630 ± 29. 969） min,AUC0-∞of（ 216. 870 ± 3. 271）,（ 150. 668 ± 7. 306）,（ 34. 883 ± 10. 245） mg·L-1·min. The tmaxand MRT0-∞of HCPT magentolipsomes（ intravenous injection） were significantly longer than those of HCPT injection（ intravenous injection）; the Cmaxand AUC0-∞of HCPT magentolipsomes（ intravenous injection） were significantly higher than those of HCPT injection（ intraperitoneal injection）. Conclusion： HCPT magentolipsomes（ intravenous injection）can evidently raise plasma concentration,bioavailability and its residence time in the body of rats,and it can protect L-HCPT from blood,which is good for the anti-tumor activity.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2017年第18期64-70,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
广东省科技计划项目(2014A020210022)
关键词
羟基喜树碱
磁性脂质体
血液微透析
高效液相色谱法
药代动力学
回收率
hydroxycamptothecin
magentolipsomes
blood microdialysis
high performance liquid chromatography（HPLC）
pharmacokinetics
recovery rate
