载异烟肼、利福平白蛋白纳米粒在兔体内的药代动力学研究  

Study on pharmacokinetics of albumin nanoparticles loaded with isoniazid and rifampicin in rabbits

作　　者：马荣[1] 陈振[1] 张惠勇[1] 梁思敏[1] 刘晓印 杨小英[3] 党宏万[3] 黑龙[1] 张党锋[4] 王自立[1] 戈朝晖[1] 

机构地区：[1]宁夏医科大学总医院骨科,银川市750004 [2]宁夏医科大学研究生院,银川市750004 [3]宁夏医科大学总医院药剂科,银川市750004 [4]西安交通大学医学院第一附属医院骨科,西安市710061

出　　处：《中国脊柱脊髓杂志》2015年第9期850-855,共6页Chinese Journal of Spine and Spinal Cord

基　　金：国家自然科学基金(30960391);宁夏自然科学基金(NZ13144)

摘　　要：目的 :研究载异烟肼(Isoniazid,INH)、利福平(Rifampicin,RFP)牛血清白蛋白(Bovine serum albumin,BSA)纳米粒经新西兰大白兔静脉给药后的体内药代动力学特征及其相关参数。方法 :16只新西兰大白兔随机分为2组:纳米粒组8只,INH、RPP对照组8只。经耳缘静脉分别滴注等计量的载INH、RFP白蛋白纳米粒和普通对照品(INH 11.43mg/kg、RFP 12mg/kg)。采用高效液相色谱分析方法测定各自INH、RFP的血浆药物浓度。对比研究静脉给药后两种剂型药物在不同时间(0、0.5、1、1.5、2、2.5、3、4、6、8、12、24、36、48、72、96、120h)兔体内的血浆药代动力学参数,包括最大血药浓度(Cmax)、生物半衰期(T1/2)、血药浓度时间曲线下的面积(AUC)及体内平均驻留时间(MRT),以DAS 2.0药动学程序进行血药浓度数据拟合分析。结果:给药后两组药物的血药浓度-时间曲线显示:纳米粒药组INH、RFP血药浓度相对稳定,药物浓度持续缓慢下降,给药后96h INH仍能检测到,RFP则为48h。INH的Cmax=9.79±1.38(mg/L),T1/2=28.10±6.69(h),AUC=22.34±8.81(mg/L·h),MRT=15.13±5.48(h);RFP的Cmax=16.79±3.74(mg/L),T1/2=14.13±3.78(h),AUC=116.64±66.26(mg/L·h),MRT=15.89±2.49(h)。对照组中INH的Cmax=9.52±2.19(mg/L),T1/2=1.92±0.80(h),AUC=20.97±3.11(mg/L·h),MRT=2.03±0.62(h);RFP的Cmax=12.50±1.58(mg/L),T1/2=2.87±0.78(h),AUC=50.05±14.50(mg/L·h),MRT=3.70±0.99(h)。对照组INH、RFP血药浓度快速下降,分别在给药后24h和12h检测不到。结论 :载异烟肼、利福平白蛋白纳米粒在兔体内的药代动力学过程符合双隔室模型(权重系数为1/cc)。白蛋白纳米粒可有效改变异烟肼和利福平的药动学行为并具有显著的缓释效果。Objectives： To study the pharmacokinetics characteristics and the relevant pharmacokinetic parameters of albumin nanoparticles loaded with isoniazid and rifampicin（INH-RFP-BSA-NPs） of the New Zealand rabbits after intravenous administration. Methods： Sixteen New Zealand rabbits were divided into 2groups randomly as below, INH-RFP-BSA-NPs group（NPs group, 8 rabbits）, control group（CON group, 8 rabbits）. The rabbits in two groups were injected with NPs and common injection of INH and RFP according to the dosage of INH 11.43mg/kg, RFP 12mg/kg via ear veins, respectively. Then blood samples were obtained at certain time points（0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120h）. High performance liquid chromatography（HPLC） was used to determine the concentrations of INH and RFP of plasma. Software program of DAS2.0 was used to study the difference of pharmacokinetic parameters. The pharmacokinetic parameters included maximal blood concentration（Cmax）, biological half-life（T1/2）, area under the time curve of blood concentration（AUC） and the mean retention time in the body（MRT）. Results： The concentration of INH and RFP in NPs group was relatively stable with a sustained decline, it could be detected at 96 hours for INH and at 48 hours for RFP respectively after administration. The isoniazid pharmacokinetic parameters of NPs were as follows： Cmax=9.79±1.38（mg/L）, T1/2=28.10±6.69（h）, AUC=22.34±8.81（mg/L·h）, MRT=15.13±5.48（h）;thoses of rifampicin were Cmax=16.79±3.74（mg/L）, T1/2=14.13±3.78（h）, AUC=116.64±66.26（mg/L·h）, MRT=15.89±2.49（h）. While in control group, the plasma concentration of INH and RFP decreased rapidly and could not be detected at 24 h and at 12 h after administration, respectively. Meanwhile the isoniazid pharmacokinetic parameters in CON group were as follows： Cmax=9.52 ± 2.19（mg/L）, T1/2=1.92 ± 0.80（h）, AUC =20.97 ± 3.11（mg/L·h）,MRT=2.03±0.62（h）; those of rifampicin were Cmax=12.50

关 键 词：异烟肼 利福平 白蛋白 纳米粒 药代动力学 

分 类 号：R529.2[医药卫生—内科学] R969.1[医药卫生—临床医学]