15例尿毒症患者应用rHuEpo的药代动力学研究

 报道了１５例尿毒症患者，ｉｖ和ｓｃｒＨｕＥｐｏ的药代动力学。用ＥＬＩＳＡ法测定血清ｒＨｕＥｐｏ浓度，用３Ｐ８７软件处理药浓度。时间数据。ｉｖ的药代动力学符合线性二室模型，其主要动力学参数Ｔ＿（１／２），Ｖ，Ｃｌ和ＡＵＣ＿（０～∞）分别为５．４５±１．４８ｈ，７９．７±５２．２ｍｌ／ｋｇ，０．３０５±０．２９８（ｍｌ·ｍｉｎ）／ｋｇ和５２９５．９±３６６１．２（ｍＵ·ｈ）／ｍｌ。ｓｃ的药代动力学符合线性一室模型，其主要的药代动力学参数Ｔ＿（ｍａｘ），Ｃ＿（ｍａｘ），Ｔ＿（１／２）和ＡＵＣ＿（０～∞）分别为１０．２±５．７ｈ，３７．２±１９．２ｍＵ／ｍｌ，１７．６±８．１ｈ和１６２０．３±８６０．７（ｍＵ·ｈ）／ｍｌ。单次ｓｃ后，血药浓度约为ｉｖ相同剂量时峰浓度的５％。占ｓｃ组５０％的患者，ｓｃ后约０．５ｈ才从血清中测到ｒＨｕＥｐｏ浓度。ｓｃ组较ｉｖ组浓度。时间曲线下总面积小。此外还比较了ｉｖ和ｓｃ的临床价值。

Pharmacokinetic studies of recombinant human erythropoietin in fifteenChinese uremic patients

We studied rHuEpo pharmacokinetics of intravenous（iv）and sbcutaneous（sc）ad-ministration in 15 uremic patients,respectively. The mean age of 8 iv and 10 sc（included 3 iv）pa-tients was 61±9 years and 46± 19 years,respectively. The mean hemoglobin of 8 iv and 10 sc ad-ministration patients was 82. 7±27.2g/L and 90. 4±21.8g/L,respectively. All patients were in-jected at 50 U/kg doses. After the first administration,serum rHuEpo level at 0,0.5,1.2,8, 12,and 24h was examined respectively in iv group and at 0.5,2,8,12,24,48 and 72 h in sc group byELISA method. The concentration-time data were analysed by using 3P87 software. The analysedresults suggested that iv administration pharmacokinetic could be described by a linear two-com-partment model and sc administration pharmacokinetic could be described by a linear single-com-partment model. The T1/2,V,Cl and AUC,which were the principle parameters of iv,Were 5. 45±1. 48 h,79. 7±52.2ml/kg,0. 305±0. 298 ml·min/kg,and 5295. 9±3661.2（mU·h）/ml,respec-tively, The Tmax:Cmax,T1/2 and AUC,which were the principle parameters of sc,were 10. 2±5.7h,37. 2±19.2mU/ml,17. 6±8.1hand 1620.3±860.7（mU·h）/ml,respectively. The T1/2 rangeof iv group and sc group was 4. 48 to 8. 02 h and 8. 65 to 35.2h,respectively.This suggested thatit is necessary for the therapy of anemia to administrate individualized dose according to the T1/2of a patient. The T1/2 of patients increased with the decrease of the Cl of patients.After single scadministration,peak serum concentrations were only about 5%of those attained by iv injection ofthe same doses. In iv administration patients,the apparent volume of the distribution of rHuEpo（V）was less than extracellular fluid volume.