载异烟肼、利福平白蛋白纳米粒中利福平在兔脊柱中的药代动力学研究  

Pharmacokinetics of Rifampicin in Rabbit Spines

作　　者：张惠勇[1] 马荣[2] 陈振[2] 刘晓印 梁思敏[2] 黑龙[2] 杨小英[3] 戈朝晖[2] 

机构地区：[1]宁夏医科大学,银川750004 [2]宁夏医科大学总医院骨科,银川750004 [3]宁夏医科大学总医院药剂科,银川750004

出　　处：《宁夏医科大学学报》2015年第4期375-379,共5页Journal of Ningxia Medical University

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、利福平白蛋白纳米粒(INH-RFP-BSA-NPs)经静脉给药后利福平(rifampicin,RFP)在兔脊柱及椎旁肌组织中的药代动力学特性。方法选取60只新西兰大白兔,分为两组,经耳缘静脉分别注射载异烟肼、利福平白蛋白纳米粒与利福平对照品,采用RP-HPLC法(reversed-phase high-performance liquid chromatography)检测各时间点椎体和椎旁肌组织中利福平的药物浓度,并用DAS 3.2.1软件计算药代动力学参数。结果实验组利福平达峰浓度(Cmax)高于对照组(P<0.05或<0.01),椎体和椎旁肌组织中浓度时间-曲线下面积(AUC0→∞)也显著高于对照组(P<0.01),半衰期(t1/2)延长(P<0.01),平均驻留时间(MRT0→∞)延长(P<0.01)。各时间点实验组兔脊柱及椎旁肌中利福平浓度均高于对照组,并且实验组在给药后36h仍能测到兔椎体中利福平浓度,椎旁肌中药物浓度可延续至96h,而对照组分别于12h、48h兔椎体、椎旁肌中已检测不到利福平药物浓度。结论与利福平普通制剂相比,载双药纳米粒使利福平在兔脊柱及椎旁肌中驻留时间延长,明显提高了椎体、椎旁肌中的药物分布。Objective To investigate the pharmacokinetics of rifampicin that released from albumin nanoparticles loaded with isoniazid and rifampicin（ INH- RFP- BSA- NPs） in rabbit＇s spines and paravertebral muscles. Methods 60 healthy New Zealand white rabbits were averagely divided into 2 groups at random. The pharmacokinetics of RFP were compared after the intravenous injection of INH- RFP- BSA- NPs and RFP solution. The drug concentration of rifampicin were detected by RP- HPLC method at each time point of vertebra and paravertebral muscle tissues. The parameters of pharmacokinetics were calculated by DAS 3. 2. 1.Results Compared with RFP solution,its Cmax was significantly higher（ P〈0. 05 or P〈0. 01） after the intravenous injection of INH- RFP- BSA- NPs,and its AUC0 → ∞ also significantly higher（ P〈0. 01）.MRT0→∞ and t1 /2 were prolonged significantly（ P〈0. 01）. At each time point,drug concentration in experimental group was slightly higher than control group. In the experimental group,that could still be detected the concentration of rifampicin in rabbit vertebral bodys after dose of 36 h. Drug concentration continued to 96 h in paraspinal muscles. In the control group,that was 12,48 h respectively. Conclusion Compared to the general formulation of rifampicin,INH- RFP- BSA- NPs extend the dwell time in the spine and paraspinal muscles. Nanoparticles can help RFP to reach long circulation activity.

关 键 词：纳米粒 利福平 脊柱 椎旁肌 高效液相色谱法 药代动力学 兔 

分 类 号：R965[医药卫生—药理学]