Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong, China.
Drug Test Anal. 2013 Jun;5(6):412-9. doi: 10.1002/dta.1444. Epub 2013 Jan 21.
Formestane (4-hydroxyandrost-4-ene-3,17-dione) is an irreversible steroidal aromatase inhibitor with reported abuse in human sports. In 2011, our laboratory identified the presence of formestane in a horse urine sample from an overseas jurisdiction. This was the first reported case of formestane in a racehorse. The metabolism of formestane in humans has been reported previously; however, little is known about its metabolic fate in horses. This paper describes the in vitro and in vivo metabolic studies of formestane in horses, with the objective of identifying the target metabolite with the longest detection time for controlling formestane abuse. In vitro metabolic studies of formestane were performed using homogenized horse liver. Seven in vitro metabolites, namely 4-hydroxytestosterone (M1), 3β,4α-dihydroxy-5β-androstan-17-one (M2a), 3β,4β-dihydroxy-5β-androstan-17-one (M2b), 3β,4α-dihydroxy-5α-androstan-17-one (M2c), androst-4-ene-3α,4,17β-triol (M3a), androst-4-ene-3β,4,17β-triol (M3b), and 5β-androstane-3β,4β,17β-triol (M4) were identified. For the in vivo studies, two thoroughbred geldings were each administered with 800 mg of formestane (32 capsules of Formadex) by stomach tubing. The results revealed that the parent drug and seven metabolites were detected in post-administration urine. The six in vitro metabolites (M1, M2a, M2b, M2c, M3a, and M3b) identified earlier were all detected in post-administration urine samples. In addition, 3α,4α-dihydroxy-5α-androstan-17-one (M2d), a stereoisomer of M2a/M2b/M2c, was also identified. This study has shown that the detection of formestane administration would be best achieved by monitoring 4-hydroxytestosterone (M1) in the glucuronide-conjugated fraction. M1 could be detected for up to 34 h post-administration. In blood samples, the parent drug could be detected for up to 34 h post administration.
福美斯坦（4-羟基雄甾-4-烯-3,17-二酮）是一种不可逆的甾体芳香酶抑制剂，据报道在人类运动中被滥用。2011 年，我们的实验室在一份来自海外司法管辖区的马尿样本中发现了福美斯坦。这是首例在赛马中发现福美斯坦的案例。福美斯坦在人体内的代谢情况此前已有报道；然而，关于其在马体内的代谢途径知之甚少。本文描述了福美斯坦在马体内的体外和体内代谢研究，旨在确定具有最长检测时间的靶代谢物，以控制福美斯坦滥用。使用马肝匀浆进行福美斯坦的体外代谢研究。鉴定出 7 种体外代谢物，即 4-羟基睾酮（M1）、3β,4α-二羟基-5β-雄甾-17-酮（M2a）、3β,4β-二羟基-5β-雄甾-17-酮（M2b）、3β,4α-二羟基-5α-雄甾-17-酮（M2c）、雄甾-4-烯-3α,4,17β-三醇（M3a）、雄甾-4-烯-3β,4,17β-三醇（M3b）和 5β-雄烷-3β,4β,17β-三醇（M4）。对于体内研究，给 2 匹纯血种公马分别经胃管给予 800mg 福美斯坦（32 粒 Formadex）。结果表明，给药后尿液中检测到母体药物和七种代谢物。之前鉴定出的六种体外代谢物（M1、M2a、M2b、M2c、M3a 和 M3b）均在给药后尿液样本中检测到。此外，还鉴定出 M2a/M2b/M2c 的立体异构体 3α,4α-二羟基-5α-雄甾-17-酮（M2d）。这项研究表明，通过监测尿中葡萄糖醛酸缀合物中 4-羟基睾酮（M1）来监测福美斯坦的给药情况最为理想。M1 可在给药后 34 小时内检测到。在血液样本中，给药后可在 34 小时内检测到母体药物。
