Sobolevsky Tim, Fedoruk Matthew, Dellanna Frank, Geyer Hans, Ahrens Brian, Thevis Mario
Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, UCLA Olympic Analytical Laboratory, Los Angeles, California, USA.
Science and Research Department, US Anti-Doping Agency, Colorado Springs, Colorado, USA.
Drug Test Anal. 2025 Jul;17(7):1088-1092. doi: 10.1002/dta.3813. Epub 2024 Oct 1.
Roxadustat (FG-4592), an orally active hypoxia-inducible factor prolyl hydroxylase stabilizer, has been shown to enhance erythropoiesis by increasing endogenous erythropoietin. It is indicated for the treatment of anemia and chronic kidney disease and is approved for clinical use in several countries, including the European Union, Japan and others. Due to its reasonably anticipated performance-enhancing effect in athletes, roxadustat is prohibited for use in sports at all times. A few cases of adverse analytical findings in routine doping controls have been reported worldwide, some of which were claimed to be the result of contaminated dietary supplements. The present study offers new data demonstrating the long-term excretion pattern of roxadustat. Even after a single-dose administration, roxadustat can remain detectable in urine for 8 months, albeit at very low concentrations (<10 pg/mL). Following three times a week treatment with 70 to 100 mg of roxadustat, the drug was still detectable in the urine of anemic patients for between 9 and 18 months after treatment was discontinued. Lastly, an athlete who admitted use of roxadustat for almost a year (50 mg 3 to 5 times a week) has now tested positive multiple times over the course of 15 months (the first test being 12 months after the drug was discontinued), with an estimated concentration of roxadustat between 3 and 8 pg/mL. Altogether, these findings indicate the unusually prolonged terminal excretion kinetics of roxadustat, a property that testing authorities should consider in their results management process.
罗沙司他（FG-4592）是一种口服活性的缺氧诱导因子脯氨酰羟化酶稳定剂，已被证明可通过增加内源性促红细胞生成素来促进红细胞生成。它被用于治疗贫血和慢性肾病，并且在包括欧盟、日本等在内的多个国家被批准用于临床。由于其在运动员身上具有合理预期的增强成绩效果，罗沙司他在体育赛事中始终被禁止使用。全球范围内已报告了几例在常规兴奋剂检测中出现不良分析结果的案例，其中一些被声称是受污染的膳食补充剂导致的。本研究提供了新的数据，证明了罗沙司他的长期排泄模式。即使单次给药后，罗沙司他在尿液中仍可检测到8个月，尽管浓度非常低（<10 pg/mL）。在用70至100毫克罗沙司他每周治疗三次后，停药后9至18个月，贫血患者的尿液中仍可检测到该药物。最后，一名承认使用罗沙司他近一年（每周3至5次，每次50毫克）的运动员在15个月内多次检测呈阳性（首次检测是在停药12个月后），罗沙司他的估计浓度在3至8 pg/mL之间。总之，这些发现表明罗沙司他具有异常延长的终末排泄动力学，检测机构在结果管理过程中应考虑这一特性。
