Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti, 1, 00197 Rome, Italy.
Anal Chim Acta. 2010 Jan 4;657(1):60-8. doi: 10.1016/j.aca.2009.10.022. Epub 2009 Oct 17.
This paper describes the effects of oral administration of non-steroidal anti-inflammatory drugs on the endogenous and synthetic anabolic androgenic steroids urinary excretion as assessed by gas-chromatography mass-spectrometry. Experiments were carried out on 5 male subjects, with pathologies and/or diseases, treated with non-steroidal anti-inflammatory drugs. To set up the individual baseline variability of testosterone and its main metabolites, urine samples were collected for 3 days, every 2 h prior to the administration of the drug(s); whereas the study of the effects of a single dose of each drug, here considered, on the endogenous androgen steroid urinary concentrations, was assessed by collecting urine samples for 2 days, every 2 h. Data obtained after drugs administration were then evaluated taking into account the individual baseline variability. The results showed that, only in the case of propyphenazone administration, the relative urinary concentrations of some testosterone metabolites were significantly altered. More specifically, the urinary levels of dehydroepiandrosterone, 11keto-etiocholanolone, 11beta-hydroxyandrosterone, 11beta-hydroxyetiocholanolone, androsterone, etiocholanolone and some metabolite ratios decrease significantly, generally between 2 and 10 h after administration of the drug, whereas no effects were observed on urinary calculated concentrations of testosterone, epitestosterone, 5alpha-androstane-3alpha,17beta-diol, 5beta-androstane-3alpha,17beta-diol and testosterone/epitestosterone ratio. The observed effects do not depend on alterations on pharmacokinetics (excretion/metabolism), but on steroid sample preparation steps (hydrolysis and derivatization) inhibition. More specifically the significant decrease of dehydroepiandrosterone and testosterone metabolites urinary levels was due to a reduced yield of the steroid derivatization step for the presence in urine of the main metabolites of propyphenazone, namely hydroxyl-propyphenazone metabolites.
本文描述了通过气相色谱-质谱法评估口服非甾体抗炎药对内源性和合成的雄性同化甾体激素尿排泄的影响。实验在 5 名患有病理和/或疾病的男性受试者中进行，他们接受了非甾体抗炎药的治疗。为了建立睾酮及其主要代谢物的个体基线变异性，在给药前每 2 小时收集 3 天的尿样；而研究单次给予每种药物（在此考虑）对内源性雄激素类固醇尿浓度的影响，则通过每 2 小时收集 2 天的尿样来评估。给药后获得的数据然后考虑个体基线变异性进行评估。结果表明，仅在丙苯酮给药的情况下，一些睾酮代谢物的相对尿浓度发生了显著变化。具体来说，脱氢表雄酮、11-酮-etiocholanolone、11β-羟基雄甾酮、11β-羟基 etiocholanolone、androsterone、etiocholanolone 和一些代谢物比值的尿水平显著降低，通常在给药后 2 至 10 小时内，而对尿中计算的睾酮、表睾酮、5α-雄烷-3α，17β-二醇、5β-雄烷-3α，17β-二醇和睾酮/表睾酮比值没有影响。观察到的影响不依赖于药代动力学（排泄/代谢）的改变，而是依赖于类固醇样品制备步骤（水解和衍生化）的抑制。具体来说，脱氢表雄酮和睾酮代谢物尿水平的显著降低是由于丙苯酮的主要代谢物，即羟基丙苯酮代谢物，存在于尿液中，导致类固醇衍生化步骤的产率降低。
