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

English Keywords:Isoniazid  Rifampicin  Albumin  Nanoparticles  Pharmacokinetics

English Abstract:

  【Abstract】 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 2 groups 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 24h and at 12h 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±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). Conclusions: The INH-RFP-BSA-NPs pharmacokinetics in rabbits process in line of double compartment model, albumin nanoparticles can effectively improve the pharmacokinetic behavior and has the advantage of significant prolonged release effect in vivo．