目的 對國產重組人促紅素注射液（濟脈欣）與進口同類型制劑Eprex^®在大鼠體內的藥動學進行對比研究，為實現(xiàn)臨床替代提供依據(jù)。方法 采用¹²⁵I標記示蹤方法測定藥物濃度，采用DAS2.0進行藥動學參數(shù)的計算，在大鼠體內分別進行單次sc 2 000 U/kg濟脈欣和Eprex^®的血漿藥物動力學對比研究、藥物組織分布對比研究和尿、糞、膽汁排泄對比研究。結果 大鼠sc相同劑量（2 000 U/kg）的濟脈欣和Eprex^®后，RA法所得血漿動力學參數(shù)：t_1/2分別為（15.8±1.67）和（15.6±3.15）h；C_max分別為（2 527±471）和（2 470±598）mU/mL；t_max分別為（10.3±1.51）和（9.00±2.45）h；AUC_0-t分別為（64 196±12 544）和（59 630±9 391）mU/mL·h，TCA-RA法所得血漿動力學參數(shù)：t_1/2分別為（15.9±4.19）和（16.2±2.45）h；C_max分別為（2 201±584）和（1 907±517）mU/mL；t_max分別為（10.0±1.27）和（9.00±2.45）h；AUC_0-t分別為（53 709±11 992）和（48 519±8 623）mU/mL·h。用RA和TCA-RA法測定濟脈欣和Eprex^®給藥后2、8、24、36 h各主要臟器及組織藥物濃度，顯示大部分組織在給藥后8 h藥物含量最大，然后逐漸降低，各主要臟器及組織藥物變化趨勢與血漿藥物消除一致，沒有發(fā)現(xiàn)蓄積現(xiàn)象。大鼠sc給藥濟脈欣和Eprex^®后，在120 h內從尿中分別可回收到給藥總量的75.7%和76.2%，在糞中可回收到給藥量的14.7%和14.9%。48 h內膽汁排泄量為11.4%和10.3%。結論 國產重組人促紅素注射液濟脈欣與國外上市制劑Eprex^®大鼠sc給藥后，主要藥動學參數(shù)t_1/2、t_max、C_max和AUC_0-t基本一致，經(jīng)統(tǒng)計檢驗無差異；兩種制劑在各組織臟器內的暴露以及尿、糞、膽汁排泄對比也無差異。

Objective The pharmacokinetics of domestic recombinant human erythropoietin injection (qimaxin) and imported Eprex^® of the same type in rats were compared to provide a basis for clinical substitution. Methods The drug concentration was determined by ¹²⁵I labeling method. The pharmacokinetic parameters were calculated by DAS 2.0. Plasma pharmacokinetic comparison of sc 2 000 U/kg zymaxin and Eprex^® in rats, comparison of drug tissue distribution, and comparison of urinary, fecal and bile excretion. Results After the same dose (2 000 U/kg) of Jimaixin and Eprex^® were injected subcutaneously in rats, the plasma kinetic parameters obtained by RA method were:t_1/2 were (1.57±1.67) and (15.6±3.15) h, respectively. C_max were (2 527±471) and (2 470±598) mU/mL, respectively. T_max were (10.3±1.51) and (9.00±2.45) h, respectively. AUC_0-t were (64 196±12 544) and (59 630±9 391) mU/mL·h, respectively. Plasma kinetic parameters obtained by TCA-RA. Method t_1/2 were (15.9±4.19) and (16.2±2.45) h, respectively. C_max were (2 201±584) and (1 907±517) mU/mL, respectively. T_max was (10.0±1.27) and (9.00±2.45) h, respectively. AUC_0-t was (53 709±11 992) and (48 519±8 623) mU/mL·h, respectively. The concentrations of major organs and tissues at 2, 8, 24, and 36 h after administration of Jimaixin and Eprex^® were measured by RA and TCA-RA, indicating that most of the tissues had the highest drug content at 8 h after administration, and then gradually decreased. The trend of drug changes in all major organs and tissues were consistent with the elimination of plasma drugs, and no accumulation was observed. After administration of Jimaixin and Eprex^® in SC, rats were able to recover 75.7% and 76.2% of the total dose from the urine within 120 hours, and 14.7% and 14.9% of the dose could be recovered in the feces. The biliary excretion in 48 hours was 11.4% and 10.3%. Conclusion The main pharmacokinetic parameters t_1/2, T_max, C_max and AUC_0-t of the domestic recombinant human erythropoietin injection and the foreign marketed Eprex^® rats were basically the same, and there was no difference by statistical test. There was no difference in the exposure of the two preparations in the organs of each tissue and the comparison of urine, feces and bile excretion.