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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。
OBJECTIVE: To study the in vivo pharmacokinetics of Isoniazid (INH) and Rifampicin (RFP) -bovine serum albumin (BSA) nanoparticles after intravenous administration in New Zealand white rabbits. Its relevant parameters. Methods: Sixteen New Zealand white rabbits were randomly divided into two groups: 8 in the NP group and 8 in the INH and RPP control groups. Instillation of INH, RFP albumin nanoparticles and normal control (INH 11.43mg / kg, RFP 12mg / kg) were respectively instilled into the ear vein. Plasma concentrations of INH and RFP were determined by high performance liquid chromatography. Comparative study after intravenous administration of two types of drugs at different times (0,0.5,1,1.5,2,2.5,3,4,6,8,12,24,36,48,72,96,120h) rabbit body (Cmax), biological half-life (T1 / 2), area under the plasma concentration time curve (AUC), and mean residence time in the body (MRT) in the plasma pharmacokinetic parameters of DAS 2.0 Dynamic program for blood concentration data fitting analysis. Results: The blood concentration-time curves of the two groups showed that the concentration of INH and RFP in the nanoparticle group was relatively stable and the drug concentration continued to decrease slowly. INH was still detected 96 h after the administration, and the RFP was 48 h . Cmax of INH = 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 Cmax = 16.79 ± 3.74 (mg / L), T1 / 2 = 14.13 ± 3.78 (h), AUC = 116.64 ± 66.26 (mg / L · h), and MRT = 15.89 ± 2.49 (h). The control group had a Cmax of 9.52 ± 2.19 (mg / L), T1 / 2 = 1.92 ± 0.80 (h), AUC = 20.97 ± 3.11 (mg / L · h) and MRT = 2.03 ± 0.62 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). Control group INH, RFP plasma concentrations decreased rapidly, respectively, after administration of 24h and 12h undetectable. CONCLUSION: The pharmacokinetics of isoniazid and rifampin albumin nanoparticles in rabbits accord with the double compartmental model (weight coefficient of 1 / cc). Albumin nanoparticles can effectively change the isokinetics of isoniazid and rifampicin and have a significant sustained release effect.