Uehlinger D E, Gotch F A, Sheiner L B
Hemodialysis Research Unit, Davies Medical Center, San Francisco, CA.
Clin Pharmacol Ther. 1992 Jan;51(1):76-89. doi: 10.1038/clpt.1992.10.
Fifty-seven patients receiving chronic high-flux hemodialysis began receiving recombinant alpha-human erythropoietin (rHuEPO). The mean initial rHuEPO dose used in 54 evaluable patients was 9963 +/- 4364 U/week; the final dose was 8972 +/- 4058 U/week. Treatment over a mean period of 154 +/- 40 days (84 to 224 days) resulted in an average increase in hematocrit from 24.7% +/- 3.7% to 32.5% +/- 4.4%. We present a model for these data that describes changes in hematocrit during rHuEPO therapy and that allows simultaneous estimation of red blood cell lifespan and rHuEPO-induced increases in red blood cell production rate. Analysis of the hematocrit values of the patients with the model, by use of NONMEM, a computer program for analysis of population data, reveals a nonlinear dose-response relationship with large interindividual variability (coefficient of variation) of about 50%. The estimated mean red blood cell lifespan is 64 days, with interindividual variability of about 30% (coefficient of variation). The intraindividual random variability in hematocrit about its prediction is +/- 5% of the prediction. For clinical dose adjustment, we present a method that uses only simple calculations.
57名接受慢性高通量血液透析的患者开始接受重组人促红细胞生成素（rHuEPO）治疗。54例可评估患者使用的rHuEPO初始平均剂量为9963±4364 U/周；最终剂量为8972±4058 U/周。平均154±40天（84至224天）的治疗使血细胞比容平均从24.7%±3.7%增至32.5%±4.4%。我们给出了一个针对这些数据的模型，该模型描述了rHuEPO治疗期间血细胞比容的变化，并能同时估算红细胞寿命以及rHuEPO诱导的红细胞生成率增加情况。通过使用用于分析群体数据的计算机程序NONMEM，利用该模型对患者的血细胞比容值进行分析，结果显示存在非线性剂量反应关系，个体间变异性（变异系数）约为50%。估计的红细胞平均寿命为64天，个体间变异性约为30%（变异系数）。血细胞比容关于其预测值的个体内随机变异性为预测值的±5%。对于临床剂量调整，我们给出了一种仅使用简单计算的方法。
