P-gp抑制的羟基喜树碱纳米混悬剂口服给药后在大鼠体内药动学的研究  

Study on pharmacokinetics of HCPT nanosuspensions with ability of inhibiting P-gp in rats after oral administration

作　　者：蒲晓辉[1,2] 孙进[2] 张鹏[2] 王永军[2] 孙英华[2] 何仲贵[2] 

机构地区：[1]河南大学药学院,河南开封475004 [2]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《中国中药杂志》2011年第14期1959-1963,共5页China Journal of Chinese Materia Medica

基　　金：国家重点基础研究发展计划(973)项目(2009CB930300)

摘　　要：目的:研究羟基喜树碱(HCPT)纳米混悬剂口服给药后在大鼠体内的药代动力学。方法:采用高效液相色谱-荧光检测法(HPLC-FD)测定HCPT的血药浓度,Diamonmsil-C18色谱柱(4.6 mm×200 mm,5μm),流动相甲醇-0.3%冰醋酸(用三乙胺调pH5.0)(57∶43),流速1.0 mL.min-1;FP-920型JASCO荧光检测器,激发波长363 nm;发射波长550 nm;柱温35℃;进样量20μL。用DAS 2.0药动学程序处理HCPT的血药浓度-时间数据。结果:本测定方法HCPT在1～50μg.L-1线性关系良好,最低定量限1μg.L-1;日内、日间精密度均小于4.3%;高、中、低3个血药浓度的提取回收率分别为98.94%,95.88%,102.7%,符合体内药物分析的要求。HCPT在大鼠体内的药代动力学符合二室开放模型,Cmax为13.10μg.L-1,Tmax为0.75 h,t1/2α为8.242 h,t1/2β为136.122 h,AUC0～t为116.77μg.h.L-1,AUC0～∞为161.93μg.h.L-1。结论:本研究中的HPLC-FD专属性强,重复性好,操作简便,适合于研究HCPT在大鼠体内的药动学和药物浓度检测。本实验中的纳米混悬剂能加快HCPT口服吸收速度,为提高口服生物利用度提供了可能性。Objective： To study on pharmacokinetics of hydroxycamptothecine （HCPT） nanosuspensions in rats after oral administration. Method： The plasma concentrations of HCPT were determined by HPLC-FD. The analysis was performed on a diamonsil TM C18 column （4.6 mm×200 mm, 5 μm） with 0.3% acetic acid-triethylamine buffer （pH 5.0） and methanol （57 ∶ 43） as mobile phase. The flow rate was 1.0 mL·min-1; the excitation wave was set at 363 nm, and emission wave was set at 550 nm; the temperature was 35 ℃. All data of concentration-time of HCPT were treated with pharmacokinetics program DAS 2.0. Result： The concentration-peak area of this assay had a good linear relation in the range from 1 to 50 μg·L^-1, and the minimum limit of quantitation was 1 μg·L^-1. The inter- and intra-day precisions of HCPT were smaller than 4.3%, and the accuracy were between -5.59% and 5.59%. The recoveries of HCPT in three plasma concentrations including high, medial, low concentration were 98.94%, 95.88% and 102.69%, respectively, which was in line with the request of biopharmaceutical analysis. The plasma concentration time profiles of HCPT fitted in two-compartment models well, and the main pharmacokinetic parameters found for HCPT after oral administration were as follows： Cmax 13.10 μg·L^-1, Tmax 0.75 h, t1/2α 8.242 h, t1/2β 136.122 h, AUC0-t 116.77 μg·h·L^-1, AUC0-∞ 161.93 μg·h·L^-1. Conclusion： The HPLC-FD method was simple, with good specificity, reproducibility, and could be used to investigate the pharmacokinetics and determinate the concentration of hydroxycamptothecin. The nanosuspension in this study could accelerate the oral absorption rate of HCPT, and make improving bioavailability of HCPT possible.

关 键 词：羟基喜树碱 纳米混悬剂 口服给药 药动学 高效液相色谱一荧光检测法 

分 类 号：R96[医药卫生—药理学]