Pharmacokinetics/Pharmacodynamics of Recombinant Human Erythropoietins in Doping Control1

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.

The promise and predicament of cosmetic neurology

“…For cardiovascular systems, human erythropoietin is used to increase oxygen carrying capacities for better endurance. 12 New transfusion methods are likely to be used in this way, and, as mentioned already, sildenafil may have similar effects. 13 To enhance motor systems, athletes use anabolic steroids commonly, an issue that has preoccupied even those at the highest level of American politics.…”

Some Empirical Notes on the Epo Epidemic in Professional Cycling

“…It postulates that a high maximal oxygen uptake (VO 2 max) is a requirement for top-level athletic achievements in endurance sports such as cycling (e.g., Birkeland et al, 2000;Gore, Hahn, Burge & Telford, 1997;Varlet-Marie, Gaudard, Audran, & Bressolle, 2003). Hemoglobin (Hb) in the blood is essential in the chain of oxygen transport to the muscles.…”

Cosmetic neurology

“…Insulin-like growth factor (IGF) produced by the liver may improve the quality of life of people without disease. 19,20 Similarly, new transfusion methods, motivated by blood supply shortages and contaminants, may have implications for performance when endurance is critical. 17 In mice, injection of recombinant viruses containing the IFG-1 gene directly into muscle also increased muscle mass and strength and prevented declines observed in untreated old mice.…”