聚乙二醇化促红细胞生成素在猕猴体内的药代动力学分析

Pharmacokinetics of Polyethylene Glycol-modified Erythropoietin in Cercopithecoids

目的分析聚乙二醇(相对分子质量40000)化促红细胞生成素(PEG-EPO)在猕猴体内的药代动力学特征。方法建立检测PEG-EPO的双抗体夹心ELISA方法,并进行验证。用1、3和9mg/kg3个剂量的PEG-EPO经静脉注射猕猴,给药后各时间点检测猕猴体内的血药浓度,用DAS软件获取各剂量组药代动力学参数。结果PEG-EPO在猕猴体内的代谢过程符合二室开放模型,1、3和9mg/kg3个剂量的PEG-EPO的消除半衰期(t1/2β)分别为(51.89300±5.39558)、(42.48550±3.01606)和(56.46130±6.81932)h;AUC0～144分别为(109.32±9.82)、(236.23±36.16)和(722.55±84.31)mg/L·h。结论相对分子质量为40000的PEG修饰的EPO能显著延长其在猕猴体内的半衰期。

Objective To analyze the pharmacokinetics of polyethylene glycol-modified erythropoietin （PEG-EPO）with a relative molecular mass of 40 000 in cercopithecoids. Methods A double antibody sandwich ELISA method for determination of PEG-EPO was developed and verified. Cercopithocoids were injected i.v. with PEG-EPO at dosages of 1, 3 and 9 mg / kg respectively, and the PEG-EPO concentrations in sera at various time points were determined. The pharmacokinetic parameters in various dosage groups were obtained by DAS software. Results The metabolism of PEG-EPO in cercopithecoids was fitted to two-department open model. The t1 / 2β of PEG-EPO at dosages of 1, 3 and 9 mg / kg were （51. 893 00 ± 5. 395 58）, （42. 485 50 ± 3. 016 06）and （56. 461 30 ± 6. 819 32）h, while the AUC0～144 were（109. 32 ± 9. 82）,（236. 23 ± 36. 16）and（722. 55 ± 84. 31）mg / L·h, respectively. Conclusion The modification with PEG at a relative molecular mass of 40 000 prolonged the half-life of EPO in cercopithecoids.