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Pharmacokinetics/Pharmacodynamics of Recombinant Human Erythropoietins in Doping Control

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Abstract

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.

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Authors and Affiliations

  1. Clinical Pharmacokinetic Laboratory, Faculty of Pharmacy, University Montpellier I, Montpellier, BP 14491, 34093, Montpellier Cédex 5, France

    Emmanuelle Varlet-Marie, Aurélie Gaudard & Francoise Bressolle

  2. Biophysical Laboratory, Faculty of Pharmacy, University Montpellier I, Montpellier, France

    Michel Audran

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  1. Emmanuelle Varlet-Marie
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  2. Aurélie Gaudard
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  3. Michel Audran
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  4. Francoise Bressolle
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Correspondence to Francoise Bressolle.

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Varlet-Marie and Gaudard have equally contributed to this work and should both be considered as first authors

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Varlet-Marie, E., Gaudard, A., Audran, M. et al. Pharmacokinetics/Pharmacodynamics of Recombinant Human Erythropoietins in Doping Control. Sports Med 33, 301–315 (2003). https://doi.org/10.2165/00007256-200333040-00004

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