Pharmacokinetics of several subcutaneous doses of erythropoietin: Potential implications for blood transfusion

1. The aim of the present study was to assess the effectiveness of repeated subcutaneous low-dose recombinant human erythropoietin (rHuEPO) on paramet ers associated with improved procurement of autologous blood; a procedure r egularly used to preclude the need for homologous blood transfusion at the time of elective surgery. 2. Three groups of three volunteers each (n = 9) were administered one of t hree low doses of rHuEPO (30, 60 or 100 IU/kg bodyweight, s.c.) on days 1, 4 and 8, The plasma pharmacokinetic profile of rHuEPO was studied after the first and third injections. Statistical evaluations were intragroup and in traindividual comparisons. 3. There was a Linear relationship between maximum plasma concentration (C- max) and dose, In the overall study group, C-max and area under the curve ( AUC) were significantly decreased, while the mean residence time (MRT) and elimination half-life (t(1/2 beta)) were significantly increased on day 8 r elative to day 1. Significant and sustained increases in reticulocytes were observed after rHuEPO administration, which were maintained above the pred ose values throughout the study period. 4. In conclusion, rHuEPO, by subcutaneous repeat-dose, was eliminated more slowly and remained longer in the circulation, despite lowered plasma conce ntrations. Repeated low rHuEPO administration at doses greater than or equa l to 60 IU/kg bodyweight stimulated modest but sustained reticulocyte conce ntrations, suggesting that cost may be substantially decreased in autologou s blood donation or perioperative treatment programmes.