Pharmacokinetics/pharmacodynamics of recombinant human erythropoietins in doping control.
The purpose of this paper is: (i) to compare recombinant human erythropoietin (rHuEPO) pharmacokinetics in athletes and healthy individuals; and (ii) to report pharmacokinetic/pharmacodynamic (PK/PD) studies performed in athletes. Effect parameters in PK/PD studies included: (i) red blood cell variables (haematocrit, reticulocyte count); and (ii) markers of iron metabolism (serum soluble transferrin receptors [sTfR], ferritin [fr] and sTfR : fr ratio). To understand the choice of these markers, we first performed a brief review of the pharmacological effects of rHuEPO. Few studies have been conducted in healthy individuals and there are minimal references concerning pharmacokinetics in athletes. A 'flip-flop' phenomenon was noted after subcutaneous administration. The pharmacokinetics appeared linear from 50-1000 U/kg, but this linearity was not observed at the lowest dose of 10 U/kg. A negative-feedback loop of endogenous erythropoietin production occurred at the end of treatment. The half-life of the terminal part of the curves seemed to be slightly higher in athletes (36-42 vs 32 hours) than in untrained individuals and total clearance tended to be greater (17.5 vs 6.5 mL/h/kg). In conclusion, more investigations are needed to better understand the relationship between rHuEPO administration and changes in haematological and iron-metabolism parameters in athletes, particularly after chronic low-dose administration of rHuEPO.
Varlet-Marie
Emmanuelle
E
Clinical Pharmacokinetic Laboratory, Faculty of Pharmacy, University Montpellier I, Montpellier, France.
Gaudard
Aurélie
A
Audran
Michel
M
Bressolle
Francoise
F
D004300:Doping in Sports / Q000517:prevention & control; D004920:Erythropoiesis; D004921:Erythropoietin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006207:Half-Life; D006400:Hematocrit; D006801:Humans; D007501:Iron / Q000378:metabolism; D011994:Recombinant Proteins; D012156:Reticulocytes / Q000378:metabolism; D013177:Sports / Q000502:physiology*
D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron