PHARMACOKINETICS AND PHARMACODYNAMICS OF RECOMBINANT-HUMAN-ERYTHROPOIETIN IN ATHLETES - BLOOD-SAMPLING AND DOPING CONTROL

1 The pharmacokinetics of recombinant human erythropoietin (rHuEpo) we re initially determined in two healthy volunteers after a single subcu taneous dose (50 u kg(-1)). Twenty subjects then received repeated sub cutaneous administrations of high dose (200 u kg(-1)) rHuEpo and 10 su bjects received placebo. An immunoradiometric assay was used to measur e the concentrations of erythropoietin (Epo) in serum and urine. 2 Ser um Epo concentration-time profiles were best described by a one-compar tment open model with zero-order input. The mean elimination half-life (+/-s.d.) was 42.0 +/- 34.2 h. Clearance, uncorrected for bioavailabi lity, was 0.05 +/- 0.01 1 h(-1) kg(-1). Erythropoietin concentrations returned to normal values in serum and urine, 7 and 4 days after the l ast administration, respectively. 3 The recombinant hormone was well t olerated. Significant changes in reticulocytes and red blood cells, ha emoglobin concentrations and haematocrit were observed after administr ation of rHuEpo. In the control group, these parameters remained uncha nged. 4 The change in reticulocytes was used as an index of the therap eutic effect of rHuEpo. The concentration-effect relationship was best described by an exponential model. 5 These data show the limitations of the measurement of Epo concentrations in blood and urine samples, c ollected in athletes during competition, for antidoping control. Epo d oping can be detected only during or within 4 to 7 days of ending, a c ourse of rHuEpo.