干扰素α-2b PLGA缓释微球大鼠体内药动学研究

 目的建立酶联免疫吸附法测定干扰素α-2b在大鼠血清中的药物浓度,进行干扰素α-2b PLGA缓释微球皮下给药后的药动学和生物利用度研究。方法采用人IFNα酶联免疫试剂盒进行血清药物含量测定;并采用3P87药动学程序进行模型拟合。结果该方法在14～875 ng·L^-1内线性关系良好(r=0.994 2);平均回收率为98.09%;板内RSD为1.06%～7.54%,板间RSD为1.34%～10.35%;微球与注射剂溶液皮下给药均符合单室模型,主要药动学参数分别为:微球t_max=4 h,ρ_max=5.490×103ng·L^{-1,MRT=2.486 d,注射剂t_max=1.5 h,ρ_max=2.532×104ng·L-1,MRT=0.095 6 d。结论ELISA法灵敏度高、重复性好,可作为干扰素α-2b PLGA微球临床前药动学的检测方法;干扰素α-2b PLGA微球具有明显的缓释作用,显著提高了干扰素α-2b的生物利用度。}

Pharmacokinetics Study of Intereron α-2b PLGA Microspheres in Rats by ELISA

OBJECTIVE To develop an enzyme linked immunosorbent assay(ELISA) method for the content determination of intereron α-2b PLGA microspheres in the serum of rats and study the pharmacokinetics and bioavailability of in rats after subcutaneous administration.METHODS Human IFNα ELISA kit was used for the content determination.The pharmacokinetic compartment model were fit by 3P87 pharmacokinetic program.RESULTS he calibration curve was linear over the range of 14-875 ng·L^-1 with the correlation coefficients of 0.994 2 and the average of recovery was 98.09%.The within-plate and between-plates RSD values were 1.06%-7.54% and 1.34%-10.35%,respectively.Pharmacokinetic parameters of were as follows:tmax4 h,ρmax5.490×103 ng·L^-1,MRT 2.486 d for IFNα-2b PLGA microspheres,and t_max 1.5 h,ρ_max 2.532×10⁴ ng·L^-1,MRT 0.095 6 d for IFNα-2b solution.Pharmacokinetics data of both formulations consistent with one compartment model.CONCLUSION The ELISA method was proved to be sensitive and well reproducible and can be used successfully for the pharmacokinetics study of the IFNα-2b PLGA microspheres.Subcutaneous administration of IFNα-2b PLGA microspheres showed significant prolonged drug release and increasd bioavailability of IFNα-2b.