幼仓鼠肾细胞表达重组人红细胞生成素在猕猴中的药动学

 目的：研究幼仓鼠肾(BHK)细胞表达红细胞生成素(EPO)在猕猴体内的药动学。方法：ELISA法测定血清浓度。结果：iv200u·kg^-1后符合二室开放模型，t_1/2α和t_1/2β分别为(1.8±0.3)h和(11.3±1.7)h?Sc50，200和800u·kg^-1后符合一级吸收一室模型，t_1/2Ke分别为(10.5±3.2)h?(10.0±1.3)h和(7.4±1.0)h，吸收速率受剂量限制，t_{1/2F=8.2，P<0.05)。tmax分别为(3.0±1.2)h,(4.0±0.0)h和(5.5±1.9)h。AUC随剂量增加，Cls相近，生物利用度为0.64。结论：EPO体内总过程基本符合线性药动学，方法学与结果对人体研究有参考意义。}

Pharmacokinetics of recombinant human erythropoietin produced by baby hamster kidney cells in rhesus monkeys

OBJECTIVE: To study the pharmacokinetics of recombinant human erythropoietin (rEPO) produced by baby hamster kidney cells (BHK). METHOD: Enzyme linked immunoasorbant assay (ELISA) was used to determine the concentration of EPO in serum. RESULTS: Concentration time profile after iv of 200 u·kg^-1 of rEPO was best fitted with 2-compartmental model with t_1/2αand t_1/2β of (1.8±0.3)h and (11.3±1.7) h, respectively. Elimination t_1/2after sc of 50, 200 and 800 u·kg^-1 were (10.5±3.2)h, (10.0±1.3)h and (7.4±1.0)h, respectively. Absorption after sc appeared in dose limited with t_1/2Ke of (0.4±0.4)h, (1.1±0.6)h and (1.9±0.6)h, respectively (F=8.2, P<0.05). t_max were (3.0±1.2)h, (4.0±0.0)h and (5.5±1.9)h, respectively. Within dosage ranges,AUC increased with dose and Cl_s was similar. Bioavailability after sc was 0.64. CONCLUSION: The overall disposition of EPO was approximately linear. This methodology and results will be useful for clinical research.