@article{3021263,
    title = "Hyperhydration Effect on Pharmacokinetic Parameters and Detection Sensitivity of Recombinant Human Erythropoietin in Urine and Serum Doping Control Analysis of Males",
    author = "Athanasiadou, I. and Dokoumetzidis, A. and Voss, S.C. and El Saftawy, W. and Al-Maadheed, M. and Valsami, G. and Georgakopoulos, C.",
    journal = "EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES",
    year = "2019",
    volume = "108",
    number = "6",
    pages = "2162-2172",
    publisher = "Elsevier B.V.",
    issn = "0928-0987",
    doi = "10.1016/j.xphs.2019.01.017",
    keywords = "erythropoietin;  recombinant erythropoietin;  acrylic acid resin;  antianemic agent;  erythropoietin;  polyacrylamide gels;  recombinant erythropoietin;  recombinant protein;  sarcosine;  sarkosyl, adult;  area under the curve;  Article;  blood pressure;  breathing rate;  Caucasian;  doping;  drug absorption;  drug accumulation;  drug blood level;  drug clearance;  drug distribution;  drug identification;  drug urine level;  elimination half-life;  exploratory research;  fluid intake;  heart rate;  human;  human experiment;  hydration;  male;  maximum concentration;  normal human;  polyacrylamide gel electrophoresis;  single drug dose;  sports drink;  time to maximum plasma concentration;  urinary excretion;  biological model;  chemistry;  clinical trial;  doping;  feasibility study;  hydration status;  physiology;  prevention and control;  procedures;  reproducibility;  sensitivity and specificity;  subcutaneous drug administration, Acrylic Resins;  Adult;  Doping in Sports;  Electrophoresis, Polyacrylamide Gel;  Erythropoietin;  Feasibility Studies;  Hematinics;  Humans;  Injections, Subcutaneous;  Male;  Models, Biological;  Organism Hydration Status;  Recombinant Proteins;  Renal Elimination;  Reproducibility of Results;  Sarcosine;  Sensitivity and Specificity",
    abstract = "Excessive fluid intake, that is, hyperhydration, may be adopted by athletes as a masking method during antidoping sample collection to influence the excretion patterns of doping agents and, therefore, manipulate their detection. The aim of this exploratory study was to assess the hyperhydration effect on the detection sensitivity of recombinant human erythropoietin (rHuEPO) by sodium N-lauroyl sarcosinate (“sarkosyl”) polyacrylamide gel electrophoresis analysis. The influence of hyperhydration on the serum and urinary pharmacokinetic (PK) profiles of rHuEPO was also investigated. Seven healthy physically active nonsmoking Caucasian males participated in a 31-day clinical study comprising a baseline (days 0, 1-3, and 8-10) and a drug phase (days 15-17, 22-24, and 29-31). Epoetin beta was administered subcutaneously at a single dose of 3000 IU on days 15, 22, and 29. Hyperhydration was applied in the morning on 3 consecutive days (days 1-3, 8-10, 22-24, and 29-31), that is, 0, 24, and 48 h after first fluid ingestion. Water and a commercial sports drink were used as hyperhydration agents (20 mL/kg body weight). Serum and urinary concentration-time profiles were best described by a one-compartment PK model with zero-order absorption. Delayed absorption was observed after hyperhydration and, therefore, lag time was introduced in the PK model. Results showed no significant difference (p > 0.05) on serum or urinary erythropoietin concentrations under hyperhydration conditions. A trend for decreasing volume of distribution and increasing clearance after hyperhydration was observed, mainly after sports drink consumption. However, no significant differences (p > 0.05) due to hyperhydration for any of the serum PK parameters calculated by noncompartmental PK analysis were observed. Renal excretion of endogenous erythropoietin and rHuEPO, as reflected on the urinary cumulative amount, was increased approximately twice after hyperhydration and this supports the nonsignificant difference on the urinary concentrations. Analysis of serum and urine samples was able to detect rHuEPO up to 72 h after drug administration. The detection window of rHuEPO remained unaffected after water or sports drink ingestion. Hyperhydration had no effect on the detection sensitivity of EPO either in serum or urine samples. © 2019 American Pharmacists Association®"
}