Optimal timing of repeated rh-erythropoietin administration improves its effectiveness in stimulating erythropoiesis in healthy volunteers

被引:31
作者
Breymann, C
Bauer, C
Major, A
Zimmermann, R
Gautsch, K
Huch, A
Huch, R
机构
[1] UNIV ZURICH,DEPT OBSTET,PERINATAL PHYSIOL UNIT,CH-8006 ZURICH,SWITZERLAND
[2] UNIV ZURICH,INST PHYSIOL,CH-8006 ZURICH,SWITZERLAND
[3] UNIV ZURICH,DEPT CLIN CHEM,CH-8006 ZURICH,SWITZERLAND
关键词
pharmacodynamics; recombinant human erythropoietin; reticulocyte and red blood cell flow-cytometry; time interval; volunteers;
D O I
10.1046/j.1365-2141.1996.d01-1501.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We studied the effect of recombinant human erythropoietin (rhEPO) on erythropoiesis when given at different time intervals to healthy adults. 15 volunteers were randomly selected to receive rhEPO (2 x 300 U/kg) and parenteral iron (2 x 200 mg) either within a 24 h or 72 h interval. Controls received parenteral iron only. Maximum EPO levels were found 24 h after the first intravenous injection (day 1) with a mean value of 364 and 390 U/l for the rhEPO-treated groups. When second rhEPO administration was after 72 h (group III), volunteers showed significantly higher absolute reticulocyte counts and a higher percentage of young RNA-rich reticulocytes (HFR ratio) over several days compared to those who received rhEPO within a 24 h interval (group II), Both rhEPO-treated groups showed an increase in the mean reticulocyte cell volume. Reticulocyte haemoglobin concentration was inversely correlated with the increasing cell size with a nadir on day 8. Reticulocyte haemoglobin content showed a significant decrease in group II after day 5. Serum ferritin levels showed an inverse pattern to the rate of erythropoiesis. After an initial rise, the serum ferritin decrease was most pronounced in group III. Contrary to previous reports with oral iron supplementation functional iron deficiency was not seen during rhEPO stimulation, due to parenteral iron administration. Our data suggest that the time interval between repeated administrations of rhEPO has an important influence on its pharmacodynamics, rhEPO given within an interval of 72 h was more effective in stimulating erythropoiesis than administration within a 24 h interval for the same total dose.
引用
收藏
页码:295 / 301
页数:7
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