Pharmacokinetics/Pharmacodynamics of Recombinant Human Erythropoietins in Doping Control

Varlet-Marie, Emmanuelle; Gaudard, Aurélie; Audran, Michel; Bressolle, Francoise
February 2003
Sports Medicine;2003, Vol. 33 Issue 4, p301
Academic Journal
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.


Related Articles

  • Pharmacokinetic-Pharmacodynamic Modelling of Recombinant Human Erythropoietin in Athletes: A Population Approach. Gaudard, A. GaudardA.; Varlet-Marie, E.; Audran, M.; Gomeni, R.; Bressolle, F. // Clinical Drug Investigation;2003, Vol. 23 Issue 3, p167 

    Objective: To develop a pharmacokinetic model able to take into account the negative feedback loop of endogenous erythropoietin production observed after repeated administration of recombinant human erythropoietin (rHuEPO), and to propose a pharmacokinetic-pharmacodynamic model capable of...

  • International Nonproprietary Names. Haselbeck, Anton // WHO Drug Information;2010, Vol. 24 Issue 1, p21 

    The article discusses the biochemical properties of epoetins, which are recombinant versions of human erythropoietin. The carbohydrate structure and glycosylation process of epoetins are described. All epoetins irrespective of their International Nonproprietary Name (INN) exhibit distinct...

  • Erythropoiesis stimulating agents: approaches to modulate activity. Sinclair, Angus M. // Biologics: Targets & Therapy;2013, Vol. 7, p161 

    Recombinant human erythropoietin (rHuEPO), such as the approved agents epoetin alfa and epoetin beta, has been used successfully for over 20 years to treat anemia in millions of patients. However, due to the relatively short half-life of the molecule (approximately 8 hours), frequent dosing may...

  • Pharmacokinetics of darbepoetin alfa after single, intravenous or subcutaneous administration in Japanese pediatric patients with chronic kidney disease. Uemura, Osamu; Hattori, Motoshi; Hataya, Hiroshi; Ito, Shuichi; Ito, Naoko; Akizawa, Tadao // Clinical & Experimental Nephrology;Dec2014, Vol. 18 Issue 6, p932 

    Background: Darbepoetin alfa (DA) is beneficial for pediatric patients for its less injection frequency and greater maximum dose compared to recombinant human erythropoietin. Here, we evaluated pharmacokinetics of DA in Japanese pediatric patients with chronic kidney disease (CKD). Methods: CKD...

  • Pharmacokinetics and Pharmacodynamics of Recombinant Human EPO-Fc Fusion Protein In Vivo. Shi, Xunlong; Yang, Jianjun; Zhu, Haiyan; Ye, Li; Feng, Meiqing; Li, Jiyang; Huang, Hai; Tao, Qun; Ye, Dan; Sun, Lee-Hwei K.; Sun, Bill N. C.; Sun, Cecily R. Y.; Han, Guizhen; Liu, Yuanyuan; Yao, Minghui; Zhou, Pei; Ju, Dianwen // PLoS ONE;Aug2013, Vol. 8 Issue 8, p1 

    In this study, the in vivo pharmacokinetics and pharmacodynamics of a novel recombinant human erythropoietin (rhEPO) Fc fusion protein, rhEPO-Fc, were studied in both rodents and rhesus monkeys. Animal models of anemia induced by irradiation, cyclophosphamide and partial renal ablation were...

  • Erythropoietin Abuse and Erythropoietin Gene Doping: Detection Strategies in the Genomic Era. Diamanti-Kandarakis, Evanthia; Konstantinopoulos, Panagiotis A.; Papailiou, Joanna; Kandarakis, Stylianos A.; Andreopoulos, Anastasios; Sykiotis, Gerasimos P. // Sports Medicine;2005, Vol. 35 Issue 10, p831 

    The administration of recombinant human erythropoietin (rhEPO) increases the maximum oxygen consumption capacity, and is therefore abused as a doping method in endurance sports. The detection of erythropoietin (EPO) abuse is based on direct pharmacological and indirect haematological approaches,...

  • The Use of Soluble Transferrin Receptor in the Detection of rHuEPO Abuse in Sports. McGrowder, Donovan; Brown, Paul; Alexander-Lindo, Ruby Lisa; Budall, Shirley; Irving, Rachael; Gordon, Lorenzo // Biochemistry Insights;2010, Issue 3, p7 

    Erythropoietin (EPO) increases the number of circulating erythrocytes and muscle oxygenation. The recombinant forms of EPO have indiscriminately been used by athletes, mainly in endurance sports to increase their erythrocytes concentration, thus generating a better delivery of oxygen to the...

  • Pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin-loaded poly(lactic-co-glycolic acid) microspheres in rats. Zhou, Xiang-lian; He, Jin-tian; Du, Hui-juan; Fan, Yang-yang; Wang, Ying; Zhang, Hong-xia; Jiang, Yang // Acta Pharmacologica Sinica;Jan2012, Vol. 33 Issue 1, p137 

    Aim:To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats.Methods:The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method....

  • Pharmacokinetic and Pharmacodynamic Comparison of Two Recombinant Human Erythropoietin Formulations, PDA10 and Eprex, in Healthy Korean Male Volunteers: A Randomized, Double-Blinded, Single-Dose, Two-Period Crossover Study. Oh, MinKyung; Yoon, Jaeseung; Cho, Doo-Yeoun // Clinical Drug Investigation;Oct2015, Vol. 35 Issue 10, p659 

    Background and Objectives: A new biosimilar human recombinant epoetin alfa product (PDA10) has been developed by PanGen Biotech Inc., Korea. This study was planned to demonstrate the pharmacokinetic and pharmacodynamic comparability of PDA10 to an existing epoetin alfa (Eprex) after a single...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics