期刊
XENOBIOTICA
卷 49, 期 7, 页码 811-822出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/00498254.2018.1504257
关键词
[14C]lesinurad; absolute bioavailability; human; disposition; accelerated mass spectrometry (AMS); epoxide hydrolase
The objectives of this study were to determine the absolute bioavailability of lesinurad and to characterized its disposition in humans. The oral bioavailability assessment was performed using a clinical design of simultaneous dosing of a therapeutic oral dose of lesinurad with an intravenous infusion of [C-14]lesinurad microdose. The bioavailability of lesinurad was determined to be 100%. The disposition of lesinurad in humans involves hepatic oxidation and renal elimination following administration of oral [C-14]lesinurad dose. Metabolism of lesinurad occurred post-systemically with low circulating levels of metabolites In vitro metabolism studies identified CYP2C9 as the predominant isoform, and summation of metabolites indicated that it was responsible for similar to 50% of metabolism.
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