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引用本文:倪利锋,曾义英,曾昭武,周晓晓,张娜娜,陈枢青.伊立替康脂质体的血浆药物含量检测及药动学研究[J].中国现代应用药学,2019,36(5):551-557.
NI Lifeng,ZENG Yiying,ZENG Zhaowu,ZHOU Xiaoxiao,ZHANG Nana,CHEN Shuqing.Study of Drug Content Detection Method in Plasma and Plasma Pharmacokinetic of Irinotecan Liposome[J].Chin J Mod Appl Pharm(中国现代应用药学),2019,36(5):551-557.
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伊立替康脂质体的血浆药物含量检测及药动学研究
倪利锋1, 曾义英2, 曾昭武2, 周晓晓2, 张娜娜2, 陈枢青1
1.浙江大学药学院, 杭州 310000;2.杭州师范大学, 杭州 310000
摘要:
目的 考察伊立替康脂质体大鼠血浆药物浓度随时间变化趋势和药动学参数,并与伊立替康注射液进行比较,评价伊立替康脂质体药动学特性。方法 大鼠尾静脉注射给予伊立替康脂质体注射液,给药剂量分别为5,10,20 mg·kg-1,对照组给予伊立替康注射液20 mg·kg-1。采用HPLC检测大鼠血浆中伊立替康含量。采用DAS 3.0软件,按药动学模块非房室模型计算分析药动学参数。采用SPSS 18.0软件进行药动学参数的统计分析。结果 伊立替康血浆对照品溶液在0.20~100.02 μg·mL-1内线性良好,r=0.999 3。与伊立替康注射液相比,伊立替康脂质体注射液的血浆达峰浓度Cmax显著提高(82倍),平均滞留时间MRT(0-t)显著延长(14.6倍),半衰期t1/2显著延长(6.5倍),总伊立替康血浆暴露量极大提高(748.5倍),经统计学分析均有显著性差异。结论 伊立替康脂质体注射液的药动学参数与伊立替康注射液相比有显著改善,可达到增强药效的目的。
关键词:  伊立替康  高效液相色谱法  脂质体  药动学  血药浓度
DOI:10.13748/j.cnki.issn1007-7693.2019.05.008
分类号:R917.101
基金项目:
Study of Drug Content Detection Method in Plasma and Plasma Pharmacokinetic of Irinotecan Liposome
NI Lifeng1, ZENG Yiying2, ZENG Zhaowu2, ZHOU Xiaoxiao2, ZHANG Nana2, CHEN Shuqing1
1.College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310000, China;2.Hangzhou Normal University, Hangzhou 310000, China
Abstract:
OBJECTIVE To investigate the plasma drug concentration and pharmacokinetic parameters in rats after intravenous injection of irinotecan liposome, and to evaluate the pharmacokinetic characteristics of irinotecan liposome compared with irinotecan injection. METHODS The dosages of irinotecan liposome injection were 5, 10 and 20 mg·kg-1, respectively. The dose of irinotecan injection in the control group was 20 mg·kg-1. The HPLC method was used to detect the irinotecan content in the rat plasma. The pharmacokinetic parameters were calculated by the non-atrioventricular model of the pharmacokinetic template in DAS 3.0 software. The statistical analysis of pharmacokinetic parameters was carried out with SPSS 18.0 software. RESULTS The control solution of irinotecan in plasma was well linear in the range of 0.20-100.02 μg·mL-1, r=0.999 3. Compared with irinotecan injection at the same dose, the plasma peak concentration Cmax of the irinotecan liposome was significantly increased(82 times), the average residence time MRT(0-t) was significantly prolonged(14.6 times), the half-life t1/2 was prolonged(6.5 times), and the total irinotecan plasma exposure was greatly increased(748.5 times). And they had significant difference by statistics analysis. CONCLUSION Compared with irinotecan injection, the pharmacokinetics of irinotecan liposome are significantly improved, may enhance the efficacy of irinotecan.
Key words:  irinotecan  HPLC  liposome  pharmacokinetics  plasma concentration
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