目的 對(duì)國(guó)產(chǎn)重組人促紅素注射液（濟(jì)脈欣）與進(jìn)口同類型制劑Eprex^®在大鼠體內(nèi)的藥動(dòng)學(xué)進(jìn)行對(duì)比研究，為實(shí)現(xiàn)臨床替代提供依據(jù)。方法 采用¹²⁵I標(biāo)記示蹤方法測(cè)定藥物濃度，采用DAS2.0進(jìn)行藥動(dòng)學(xué)參數(shù)的計(jì)算，在大鼠體內(nèi)分別進(jìn)行單次sc 2 000 U/kg濟(jì)脈欣和Eprex^®的血漿藥物動(dòng)力學(xué)對(duì)比研究、藥物組織分布對(duì)比研究和尿、糞、膽汁排泄對(duì)比研究。結(jié)果 大鼠sc相同劑量（2 000 U/kg）的濟(jì)脈欣和Eprex^®后，RA法所得血漿動(dòng)力學(xué)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(dòng)力學(xué)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(cè)定濟(jì)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(shì)與血漿藥物消除一致，沒(méi)有發(fā)現(xiàn)蓄積現(xiàn)象。大鼠sc給藥濟(jì)脈欣和Eprex^®后，在120 h內(nèi)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(nèi)膽汁排泄量為11.4%和10.3%。結(jié)論 國(guó)產(chǎn)重組人促紅素注射液濟(jì)脈欣與國(guó)外上市制劑Eprex^®大鼠sc給藥后，主要藥動(dòng)學(xué)參數(shù)t_1/2、t_max、C_max和AUC_0-t基本一致，經(jīng)統(tǒng)計(jì)檢驗(yàn)無(wú)差異；兩種制劑在各組織臟器內(nèi)的暴露以及尿、糞、膽汁排泄對(duì)比也無(wú)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.