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PHARMACOKINETICS OF SEVERAL SUBCUTANEOUS DOSES OF ERYTHROPOIETIN: POTENTIAL IMPLICATIONS FOR BLOOD TRANSFUSION
Author(s) -
Sans T.,
Joven J.,
Vilella E.,
Masdeu G.,
Farrè M.
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2000.tb03078.x
Subject(s) - medicine , erythropoietin , pharmacokinetics , reticulocyte , blood transfusion , hematocrit , perioperative , anesthesia , urology , surgery , biochemistry , chemistry , messenger rna , gene
1 The aim of the present study was to assess the effectiveness of repeated subcutaneous low‐dose recombinant human erythropoietin (rHuEPO) on parameters associated with improved procurement of autologous blood; a procedure regularly 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 three low doses of rHuEPO (30, 60 or 100 IU/kg body weight, 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 intra‐individual 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 1/2β ) were significantly increased on day 8 relative to day 1. Significant and sustained increases in reticulocytes were observed after rHuEPO administration, which were maintained above the predose 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 concentrations. Repeated low rHuEPO administration at doses ≥ 60 IU/kg bodyweight stimulated modest but sustained reticulocyte concentrations, suggesting that cost may be substantially decreased in autologous blood donation or perioperative treatment programmes.