Thevis Mario, Geyer Hans, Mareck Ute, Flenker Ulrich, Schänzer Wilhelm
Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.
Ther Drug Monit. 2007 Apr;29(2):236-47. doi: 10.1097/FTD.0b013e31803bb85d.
5alpha-Reductase inhibitors such as finasteride are prohibited in sports according to the World Anti-Doping Agency. This class of drugs is used therapeutically to treat benign prostatic hyperplasia, as well as male baldness, by decreasing 5alpha-reductase activity. Accordingly, metabolic pathways of endogenous as well as synthetic steroids are influenced, which complicates the evaluation of steroid profiles in sports drug testing. The possibility of manipulating steroid excretion profiles and, presumably, to mask steroid abuse was investigated in 5 administration studies with use of finasteride at different doses, with and without coadministration of 19-norandrostenedione. The evaluation of urinary steroid profiles demonstrated the intense effect of finasteride on numerous crucial analytical parameters, in particular the production of 5alpha-steroids such as androsterone and 5alpha-androstane-3alpha,17beta-diol, which was significantly reduced. In addition, the excretion of the main metabolite of norandrostenedione, norandrosterone, was significantly suppressed, by up to 84%, in elimination studies. For doping-control analysis the use of 5alpha-reductase inhibitors causes considerable problems because steroid profile parameters, which are commonly considered stable, are highly affected and complicate the detection of steroid abuse. In addition, the suppression of production and renal excretion of 5alpha-steroids such as 19-norandrosterone generated from anabolic agents such as 19-norandrostenedione may lead to false-negative doping-control results, because urine specimens are reported positive only when a threshold level of 2 ng/mL is exceeded. Finally, a method for the determination of the major urinary metabolite of finasteride (carboxy-finasteride) in routine doping-control screening with use of liquid chromatography-tandem mass spectrometry is described, allowing the detection of carboxy-finasteride for up to 94 hours in urine specimens collected after an oral administration of 5 mg of finasteride.
根据世界反兴奋剂机构的规定，非那雄胺等5α-还原酶抑制剂在体育赛事中被禁用。这类药物在治疗上用于治疗良性前列腺增生以及男性秃发，通过降低5α-还原酶的活性来实现。因此，内源性和合成类固醇的代谢途径都会受到影响，这使得在体育药物检测中对类固醇谱的评估变得复杂。在5项给药研究中，研究了使用不同剂量非那雄胺（无论是否同时给予19-去甲雄烯二酮）对类固醇排泄谱进行操纵以及可能掩盖类固醇滥用的可能性。尿类固醇谱的评估表明，非那雄胺对众多关键分析参数有强烈影响，特别是对5α-类固醇如雄酮和5α-雄甾烷-3α,17β-二醇的生成有显著抑制作用。此外，在消除研究中，去甲雄烯二酮的主要代谢产物去甲雄酮的排泄被显著抑制，最高可达84%。对于兴奋剂检测分析而言，使用5α-还原酶抑制剂会引发相当大的问题，因为通常被认为稳定的类固醇谱参数会受到严重影响，从而使类固醇滥用的检测变得复杂。此外，对诸如19-去甲雄烯二酮等合成代谢剂产生的5α-类固醇（如19-去甲雄酮）的生成和肾脏排泄的抑制，可能会导致兴奋剂检测结果出现假阴性，因为只有当尿样中超过2 ng/mL的阈值水平时才会报告为阳性。最后，描述了一种使用液相色谱-串联质谱法在常规兴奋剂检测筛查中测定非那雄胺主要尿代谢产物（羧基非那雄胺）的方法，口服5 mg非那雄胺后收集的尿样中可检测到羧基非那雄胺长达94小时。
