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  

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

作　　者：刘秀文[1,2] 汤仲明[1,2] 屠敏[1,2] 刘钿连 

机构地区：[1]军事医学科学院放射医学研究所 [2]丽珠集团生物工程制药厂

出　　处：《中国药学杂志》1998年第9期549-552,共4页Chinese Pharmaceutical Journal

摘　　要：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，ｔ１／２α和ｔ１／２β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，ｔ１／２Ｋｅ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，ｔ１／２Ｋａ分别为（０．４±０．４）ｈ，（１．１±０．６）ｈ和（１．９±０．６）ｈ（Ｆ＝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。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1/2α and t1/2β of (1.8±0.3)h and (11.3±1.7) h, respectively. Elimination t1/2 after 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1/2Ka 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.

关 键 词：红细胞生成素 幼仓鼠紧细胞 药物动力学 猕猴 

分 类 号：R973.3[医药卫生—药品]