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首页> 外文期刊>Drug testing and analysis >Drug-drug interaction and doping, part 1: An in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene
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Drug-drug interaction and doping, part 1: An in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene

机译：药物相互作用和掺杂，第1部分：体外研究非禁用药物对托瑞米芬I期代谢谱的影响

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The present study was designed to provide preliminary information on the potential impact of metabolic drug-drug interaction on the effectiveness of doping control strategies currently followed by the anti-doping laboratories to detect the intake of banned agents. In vitro assays based on the use of human liver microsomes and recombinant CYP isoforms were designed and performed to characterize the phase I metabolic profile of the prohibited agent toremifene, selected as a prototype drug of the class of selective oestrogen receptor modulators, both in the absence and in the presence of medicaments (fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ranitidine, fluoxetine, paroxetine, nefazodone) not included in the World Anti-Doping Agency list of prohibited substances and methods and frequently administered to athletes. The results show that the in vitro model developed in this study was adequate to simulate the in vivo metabolism of toremifene, confirming the results obtained in previous studies. Furthermore, our data also show that ketoconazole, itraconazole, miconazole and nefazodone cause a marked modification in the production of the metabolic products (i.e. hydroxylated and carboxylated metabolites) normally selected by the anti-doping laboratories as target analytes to detect toremifene intake; moderate variations were registered in the presence of fluconazole, paroxetine and fluoxetine; while no significant modifications were measured in the presence of ranitidine and cimetidine. This evidence imposes that the potential effect of drug-drug interactions is duly taken into account in anti-doping analysis, also for a broader significance of the analytical results.
机译：本研究旨在提供有关代谢药物相互作用的潜在影响的初步信息，这些影响目前正在由反兴奋剂实验室用来检测违禁药物的摄入的兴奋剂控制策略的有效性。设计并进行了基于使用人肝微粒体和重组CYP同工型的体外测定，以表征被禁用药物toremifene的I期代谢谱，该药物被选作选择性雌激素受体调节剂的原型药物，两者都不存在并且在存在于世界反兴奋剂机构禁用物质和方法清单中且经常向运动员服用的药物（氟康唑，酮康唑，伊曲康唑，咪康唑，西咪替丁，雷尼替丁，氟西汀，帕罗西汀，奈法唑酮）不存在的情况下。结果表明，本研究开发的体外模型足以模拟托瑞米芬的体内代谢，证实了先前研究中获得的结果。此外，我们的数据还表明，酮康唑，伊曲康唑，咪康唑和奈法唑酮会导致代谢产物（即羟基化和羧化代谢物）的生产发生显着变化，这些代谢产物通常由反兴奋剂实验室选作目标分析物，以检测去甲替米芬的摄入量。在存在氟康唑，帕罗西汀和氟西汀的情况下，观察到中等程度的变化;在雷尼替丁和西咪替丁存在的情况下，未见明显变化。该证据表明，在反兴奋剂分析中应充分考虑药物相互作用的潜在影响，这对于分析结果也具有更广泛的意义。

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