重组人干扰素α2a在小鼠和大鼠体内i.v.和i.m.的药动学研究

Pharmacokinetic study of rh-IFNα2a in mice and rats after intravenous and intramuscular administration

目的:研究rh-干扰素α2a(rh-IFNα2a)在小鼠和大鼠体内i.v.和i.m.的血药浓度-时间曲线、药动学参数和分布、排泄特点。方法:用双抗体夹心ELISA法测rh-IFNα2a在小鼠和大鼠体内i.v.和i.m.后血清、胆汁、尿液及组织中的药物浓度,用DAS药动学统计软件进行血药浓度-时间曲线拟合及药动学参数计算,并结合免疫组织化学技术研究rh-IFNα2a的组织分布特点。结果:Rh-IFNα2a i.v.和i.m的药动学行为分别符合二室和一室开放模型,呈一级动力学消除;rh-IFNα2a主要分布在肾、肺组织中;rh-IFNα2a 36 h尿累计排泄量为0.121%,胆汁累计排泄量为0.247%。结论:I.v.i、.m.rh-IFNα2a的药动学行为分别符合二室一级消除、一室一级消除。

AIM： To study pharmacokinetic property of rh-IFNα2a after intravenous （ i. v. ） and intramuscular （i. m. ） injection to mice and rats. METHODS： Double antibody sandwich ELISA analysis was used for testing drug concentration in serum, urine, bile and tissues after i.v. and i.m. administration of rh-IFNα2a in mice and rats. Pharmacokinetic parameters were calculated by DAS software. Immunohistochemistry technique was also adopted to evaluate its distribution characters.RESULTS： Pharmacokinetic model of rh-IFNα2a after i.v. and i.m. was consistent with two-compartment and one-compartment open model respectively, both submitting to first-order kinetic elimination. Rh-IFNα2a was predominantly distributed in kidney and lung tissue. The total drug accumulative excretion quantity in urine was 0. 121% of the administered after rh-IFNα2a 8.19 μg/kg i.v. into mice. The total drug accumulative excretion quantity in bile was 0.247% of the administered after rh-IFNα2a 4.10 μg/kg i.v. into rats. CONCLUSION： Pharmacokinetic models after i.v. and i.m. rh-IFNα2a are two - compartment open model and one-compartment open model, respectively, both with first-order kinetic elimination.