Anti-Doping Lab Qatar, Sports City Road, Sports City, P.O. Box 27775, Doha, Qatar; Department of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis-Zographou, 15771 Athens, Greece.
Department of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis-Zographou, 15771 Athens, Greece.
J Pharm Sci. 2019 Jun;108(6):2162-2172. doi: 10.1016/j.xphs.2019.01.017. Epub 2019 Jan 23.
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.
过度饮水，即过度水化，可能被运动员用作兴奋剂样本采集时的一种掩盖方法，以影响兴奋剂的排泄模式，从而操纵其检测。本探索性研究的目的是评估通过 N-月桂酰肌氨酸聚丙酰胺凝胶电泳分析（sarkosyl-PAGE）对重组人促红细胞生成素（rHuEPO）检测灵敏度的过度水化影响。还研究了过度水化对 rHuEPO 的血清和尿液药代动力学（PK）谱的影响。七名健康的非吸烟白种男性在一项 31 天的临床研究中参与，该研究包括基线（第 0、1-3 和 8-10 天）和药物阶段（第 15-17、22-24 和 29-31 天）。在第 15、22 和 29 天，每天皮下给予促红素β 3000IU 单剂量。在连续 3 天（第 1-3、8-10、22-24 和 29-31 天）的早晨应用过度水化，即在首次摄入液体后 0、24 和 48 小时。水和一种商业运动饮料被用作过度水化剂（20 毫升/千克体重）。血清和尿液浓度-时间曲线最好用零级吸收的单室 PK 模型描述。过度水化后观察到吸收延迟，因此在 PK 模型中引入了滞后时间。结果表明，在过度水化条件下，血清或尿液中促红细胞生成素浓度无显著差异（p>0.05）。观察到过度水化后分布容积减小和清除率增加的趋势，主要在运动饮料消耗后。然而，通过非房室 PK 分析计算的任何血清 PK 参数，由于过度水化，都没有观察到显著差异（p>0.05）。肾内排泄内源性促红细胞生成素和 rHuEPO，反映在尿累积量上，在过度水化后增加了约两倍，这支持了尿浓度的无显著性差异。对血清和尿液样本的分析能够在药物给药后 72 小时内检测到 rHuEPO。在水或运动饮料摄入后，rHuEPO 的检测窗口保持不变。过度水化对血清或尿液样本中 EPO 的检测灵敏度均无影响。
