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非甾体抗炎药不会影响尿中睾酮/表睾酮葡萄糖醛酸苷比值。

Non-steroidal anti-inflammatory drugs do not influence the urinary testosterone/epitestosterone glucuronide ratio.

机构信息

Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet Stockholm, Sweden.

出版信息

Front Endocrinol (Lausanne). 2013 May 16;4:51. doi: 10.3389/fendo.2013.00051. eCollection 2013.

Abstract

The UDP Glucuronosyl Transferase (UGT) enzymes are important in the pharmacokinetics, and conjugation, of a variety of drugs including non-steroidal anti-inflammatory drugs (NSAIDs) as well as anabolic androgenic steroids (AAS). Testosterone glucuronidation capacity is strongly associated with a deletion polymorphism in the UGT2B17 gene. As the use of high doses of NSAIDs has been observed in athletes there is a risk for a drug-drug interaction that may influence the doping tests for AAS. In vitro studies show inhibitory potential on UGT2B7, 2B15, and 2B17 enzymes by NSAIDs. The aim of this study was to investigate if concomitant use of NSAIDs and a single dose of testosterone enanthate would affect the excretion rate of testosterone and epitestosterone glucuronide (TG and EG) as well as the T/E ratio, thereby affecting the outcome of the testosterone doping test. The study was designed as an open, randomized, cross-over study with subjects being their own control. The 23 male healthy volunteers, with either two, one or no allele (ins/ins, ins/del, or del/del) of the UGT2B17 gene, received the maximum recommended dose of NSAID (Ibuprofen or Diclofenac) for 6 days. On day three, 500 mg of testosterone enanthate was administered. Spot urine samples were collected for 17 days. After a wash-out period of 4 months the volunteers received 500 mg testosterone enanthate only, with subsequent spot urine collection for 14 days. The glucuronides of testosterone and epitestosterone were quantified. NSAIDs did not affect the excretion of TG or EG before the administration of testosterone. The concomitant use of NSAIDs and testosterone slightly increased the TG excretion while the EG excretion was less suppressed compared to testosterone use only. The effects of the NSAIDs on the TG and EG excretion did not differ between the UGT2B17 genotype groups. In conclusion, the outcome of testosterone doping tests does not seem to be affected by the use of NSAIDs.

摘要

尿苷二磷酸葡萄糖醛酸转移酶(UGT)在各种药物的药代动力学和结合中很重要,包括非甾体抗炎药(NSAIDs)和合成代谢雄激素类固醇(AAS)。睾酮葡萄糖醛酸化能力与 UGT2B17 基因的缺失多态性密切相关。由于运动员大量使用 NSAIDs,因此存在药物相互作用的风险,可能会影响 AAS 的兴奋剂检测。体外研究表明,NSAIDs 对 UGT2B7、2B15 和 2B17 酶具有抑制作用。本研究旨在探讨 NSAIDs 与单次睾酮 enanthate 合用是否会影响睾酮和表睾酮葡萄糖醛酸苷(TG 和 EG)的排泄率以及 T/E 比值,从而影响睾酮兴奋剂检测的结果。该研究设计为开放、随机、交叉研究,受试者为自身对照。23 名健康男性志愿者,携带 UGT2B17 基因的两个、一个或没有等位基因(ins/ins、ins/del 或 del/del),接受最大推荐剂量的 NSAID(布洛芬或双氯芬酸)治疗 6 天。第 3 天,给予 500mg 睾酮 enanthate。采集 17 天的点尿样。洗脱期 4 个月后,志愿者仅接受 500mg 睾酮 enanthate 治疗,随后采集 14 天的点尿样。定量检测睾酮和表睾酮的葡萄糖醛酸苷。在给予睾酮之前,NSAIDs 不影响 TG 或 EG 的排泄。与单独使用睾酮相比,同时使用 NSAIDs 和睾酮略微增加了 TG 的排泄,而 EG 的排泄抑制作用较小。NSAIDs 对 TG 和 EG 排泄的影响在 UGT2B17 基因型组之间没有差异。结论,NSAIDs 的使用似乎不会影响睾酮兴奋剂检测的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8c3/3655282/0babe6838bcc/fendo-04-00051-g001.jpg

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