OPTIMAL TIMING OF REPEATED RH-ERYTHROPOIETIN ADMINISTRATION IMPROVES ITS EFFECTIVENESS IN STIMULATING ERYTHROPOIESIS IN HEALTHY-VOLUNTEERS

We studied the effect of recombinant human erythropoietin (rhEPO) on e rythropoiesis 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 interva l. Controls received parenteral iron only. Maximum EPO levels were fou nd 24 h after the first intravenous injection (day 1) with a mean valu e of 364 and 390 U/l for the rhEPO-treated groups. When second rhEPO a dministration was after 72 h (group III), volunteers showed significan tly higher absolute reticulocyte counts and a higher percentage of you ng RNA-rich reticulocytes (HFR ratio) over several days compared to th ose who received rhEPO within a 24 h interval (group II), Both rhEPO-t reated 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 haemoglob in content showed a significant decrease in group II after day 5. Seru m ferritin levels showed an inverse pattern to the rate of erythropoie sis. After an initial rise, the serum ferritin decrease was most prono unced in group III. Contrary to previous reports with oral iron supple mentation functional iron deficiency was not seen during rhEPO stimula tion, due to parenteral iron administration. Our data suggest that the time interval between repeated administrations of rhEPO has an import ant influence on its pharmacodynamics, rhEPO given within an interval of 72 h was more effective in stimulating erythropoiesis than administ ration within a 24 h interval for the same total dose.