Tanaka H, Tokiwa T
Pharmaceutical Development Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
J Pharmacol Exp Ther. 1990 Nov;255(2):724-9.
A sandwich enzyme-linked immunosorbent assay for the measurement of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rat serum was developed using anti-rhG-CSF Fab'-horseradish peroxidase conjugate. This assay method measured rhG-CSF in rat serum with greater sensitivity than a bioassay. Also, a good agreement between enzyme-linked immunosorbent assay and bioassay was observed with rat serum samples after administration of rhG-CSF. The pharmacokinetics of rhG-CSF were investigated in male Sprague-Dawley rats using enzyme-linked immunosorbent assay at four different doses from 1 to 100 micrograms/kg. For i.v. administration, the serum rhG-CSF concentration-time curves were best described by a biexponential equation. Over the dose range studied, no changes in volume of distribution were observed. However, a reduction in rhG-CSF clearance and prolongation of half-life (beta) were noted as the dose of rhG-CSF increased. For s.c. administration, a markedly lower serum peak rhG-CSF concentration was observed, but after 2 to 3 hr, rhG-CSF concentration was higher than that following i.v. administration. Administration s.c. also caused nonlinear increases in the serum concentration. Bioavailability after s.c. administration was 0.509 to 0.704.
利用抗重组人粒细胞集落刺激因子（rhG-CSF）Fab'-辣根过氧化物酶偶联物，建立了一种夹心酶联免疫吸附测定法，用于检测大鼠血清中的重组人粒细胞集落刺激因子（rhG-CSF）。该测定方法检测大鼠血清中rhG-CSF的灵敏度高于生物测定法。此外，在给予rhG-CSF后，酶联免疫吸附测定法与生物测定法对大鼠血清样本的检测结果具有良好的一致性。使用酶联免疫吸附测定法，在1至100微克/千克的四种不同剂量下，对雄性Sprague-Dawley大鼠体内rhG-CSF的药代动力学进行了研究。静脉注射给药时，血清rhG-CSF浓度-时间曲线最适合用双指数方程描述。在所研究的剂量范围内，未观察到分布容积的变化。然而，随着rhG-CSF剂量的增加，rhG-CSF清除率降低，半衰期（β）延长。皮下注射给药时，观察到血清rhG-CSF峰值浓度明显较低，但在2至3小时后，rhG-CSF浓度高于静脉注射给药后的浓度。皮下注射给药还导致血清浓度呈非线性增加。皮下注射给药后的生物利用度为0.509至0.704。
