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A pharmacodynamic model of erythropoietin therapy for uremic anemia
Author(s) -
Uehlinger Dominik E,
Gotch Frank A,
Sheiner Lewis B
Publication year - 1992
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1992.10
Subject(s) - hematocrit , nonmem , medicine , erythropoietin , anemia , hemodialysis , pharmacodynamics , population , coefficient of variation , red blood cell , physiology , pharmacokinetics , chemistry , environmental health , chromatography
Fifty‐seven patients receiving chronic high‐flux hemodialysis began receiving recombinant a‐human erythropoietin (rHuEPO). The mean initial rHuEPO dose used in 54 évaluable 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. Clinical Pharmacology and Therapeutics (1992) 51 , 76–89; doi: 10.1038/clpt.1992.10