University Hospital of Padova, Padova, Italy.
Department of Cardiac Thoracic and Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Drug Test Anal. 2019 Jun;11(6):762-771. doi: 10.1002/dta.2555. Epub 2018 Dec 25.
Letrozole is an aromatase inhibitor, used to treat postmenopausal women with hormone receptor-positive or unknown advanced breast cancer. It is prohibited in sport because it is used together with androgen anabolizing steroids to avoid their adverse effects. In the case of an adverse analytical finding, it may be important to distinguish between repetitive use due to voluntary administration and occasional use, possibly due to involuntary intake. With the objective to identify the dose capable of producing a positive hair test, and to apply these results to the scenarios of inadvertent letrozole ingestion by an athlete, this study investigates the urinary excretion and incorporation into hair of single doses of letrozole. Seven subjects were recruited for an excretion study of letrozole and its metabolite bis(4-cyanophenyl) methanol (M1) in urine, after the consumption of 0.62 mg, 1.25 mg, and 2.5 mg of letrozole, and to investigate the incorporation in hair after ingestion of 0.62 mg and 2.5 mg of letrozole. Urine and hair samples were also obtained from two women in chronic therapy. Urinary concentrations of letrozole and its metabolite M1 were lower in subjects administered once with 0.62 mg, 1.25 mg, or 2.5 mg letrozole than in women in regular therapy with 2.5 mg/day. In hair collected after a single dosage, concentrations of 16-60 pg/mg were detected while in women in chronic therapy concentrations were higher than 160 pg/mg all along the hair shaft. Hair analysis turned to be a promising possibility for the discrimination of letrozole repetitive use vs occasional/inadvertent administration.
来曲唑是一种芳香化酶抑制剂，用于治疗激素受体阳性或未知的绝经后晚期乳腺癌。它在运动中被禁用，因为它与雄激素同化类固醇一起使用，以避免它们的不良影响。在出现不良分析结果的情况下，区分由于自愿给药而重复使用和偶尔使用（可能是由于非自愿摄入）可能很重要。本研究旨在确定能够产生阳性毛发检测结果的剂量，并将这些结果应用于运动员意外摄入来曲唑的情况，以调查单次剂量来曲唑及其代谢物双（4-氰基苯基）甲醇（M1）在尿液中的排泄和在头发中的掺入情况。在摄入 0.62mg、1.25mg 和 2.5mg 来曲唑后，招募了 7 名受试者进行来曲唑及其代谢物 M1 的排泄研究，并在摄入 0.62mg 和 2.5mg 来曲唑后研究其在头发中的掺入情况。还从两名接受慢性治疗的女性中获得了尿液和头发样本。与定期接受 2.5mg/天治疗的女性相比，单次给予 0.62mg、1.25mg 或 2.5mg 来曲唑的受试者的尿液中来曲唑及其代谢物 M1 的浓度较低。单次剂量后收集的头发中检测到 16-60pg/mg 的浓度，而在慢性治疗的女性中，整个发束中的浓度均高于 160pg/mg。毛发分析有望成为区分来曲唑重复使用与偶然/意外给药的一种有前途的方法。
