摘要
目的研究丝裂霉素两亲性壳聚糖聚合物胶束在大鼠体内药动学和组织分布特征。方法 Wistar大鼠分别尾静脉注射0.5 mg·kg-1市售注射用丝裂霉素和丝裂霉素两亲性壳聚糖聚合物胶束,采用超快速液相色谱-串联质谱联用法(UPLC-MS/MS)测定大鼠血浆和组织中丝裂霉素的浓度。结果注射用丝裂霉素和丝裂霉素两亲性壳聚糖聚合物胶束在大鼠体内的t1/2(β)分别为(0.67±0.363)和(3.33±1.47)h,AUC0→∞分别为(120.94±13.77)和(140.95±11.56)h·ng·mL-1,MRT分别为(0.829±0.128)和(1.56±0.215)h,CL分别为(5.002±1.003)和(3.001±1.000)mL·h-1·kg-1。丝裂霉素两亲性壳聚糖聚合物胶束在大鼠心脏、肝脏、脾脏、肺脏和肾脏中的分布均低于注射用丝裂霉素,其中药物在肝脏、脾脏和肾脏中的分布有显著性降低。结论丝裂霉素两亲性壳聚糖聚合物胶束能延长丝裂霉素在体内的作用时间,提高生物利用度,显著降低药物的肝、肾毒性。
ABSTRACT ： OBJECTIVE To investigate the pharmacokinetics and tissue distribution of mitomycin amphiphilic chitosan polymeric micelles （MMC-ACPM） in rats. METHODS Mitomycin injection （MMC-INJ） and MMC-ACPM were administered to rats through tail vein at the dosage of 0. 5 mg ·kg-1. An ultra-fast liquid chromatography with tandem mass spectrometry （UPLC-MS/MS） method was established to determine the concentration of mitomycin （MMC） in plasma and tissues of rats. RESULTS The tl/2of MMC-INJ and MMC-ACPM in plasma were estimated to be （0. 67 ±0. 36） and （3.33 ± 1.47） h, respectively. The AUC0→∞were calculated to be （ 120. 94 ± 13.77） and （ 140. 95± 11.56） mL-h-1·kg-1 , respectively. The MRT were （0. 83 ±0. 13） and （ 1.56 ±0. 22） h, and CL were （0. 005 ± 0. 001 ） and （0. 003 ± 0. 001 ）mL-h-1·kg-1 , respectively. Compared with MMC-INJ group, MMC-ACPM group had lower concentrations of MMC in heart, liver, spleen, lung, and kidney of rats. CONCLUSION MMC-ACPM can prolong the circulation of MMC in vivo, improve its bioavailability, and reduce the accumulation in liver and kidney, which can improve curative effects and reduce toxicity.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2013年第18期1569-1573,共5页
Chinese Pharmaceutical Journal
关键词
丝裂霉素
两亲性壳聚糖衍生物
聚合物胶束
药动学
组织分布
mitomycin
amphiphilic chitosan derivative
polymeric micelle
pharmacokinetics
tissue distribution
