Hyperhydration effect on pharmacokinetic parameters and detection sensitivity of recombinant human erythropoietin in urine and serum doping control analysis of males / Ioanna Athanasiadou, Aristeidis Dokoumetzidis, Sven Christian Voss, Wesal El Saftawy, Mohammed Al-Maadheed, Georgia Valsami, Costas Georgakopoulos. - (Journal of pharmaceutical sciences (2019, 23 January)) .
- PMID: 30684541.
- DOI: 10.1016/j.xphs.2019.01.017
Abstract:
Excessive fluid intake, i.e., hyperhydration may be adopted by athletes as a masking method during anti-doping 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 SAR-PAGE analysis. The influence of hyperhydration on the serum and urinary pharmacokinetic (PK) profiles of rHuEPO was also investigated. Seven healthy physically active non-smoking Caucasian males were participated in a 31-day clinical study comprised a baseline (Days 0, 1‒3, 8‒10) and a drug phase (Days 15‒17, 22‒24, 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 three consecutive days (Days 1‒3, 8‒10, 22‒24, 29‒31), i.e., 0, 24 and 48 hours 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 (Tlag) was introduced in the PK model. Results showed no significant difference (P > 0.05) on serum or urinary EPO 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 Non-Compartmental PK Analysis were observed. Renal excretion of endogenous and rHuEPO, as reflected on the urinary cumulative amount, was increased approximately twice after hyperhydration and this supports the non-significant difference on the urinary concentrations. Analysis of serum and urine samples was able to detect rHuEPO up to 72 hours 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.
