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Xenobiotica. 2019 Jul;49(7):811-822. doi: 10.1080/00498254.2018.1504257. Epub 2018 Sep 12.

Metabolism and disposition of lesinurad, a uric acid reabsorption inhibitor, in humans.

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a Preclinical and Clinical DMPK , San Diego , CA , USA.
b Bioanalytical Development Ardea Biosciences, Inc. , San Diego , CA , USA.
c Clinical Development Ardea Biosciences, Inc. , San Diego , CA , USA.
d Early Clinical Development, IMED Biotech Unit , Quantitative Clinical Pharmacology, AstraZeneca LP , Gaithersburg , MD , USA.


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 [14C]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 [14C]lesinurad dose. Metabolism of lesinurad occurred post-systemically with low circulating levels of metabolites <3% of total radioactivity as 74.2% of total radioactivity was attributed to lesinurad. In vitro metabolism studies identified CYP2C9 as the predominant isoform, and summation of metabolites indicated that it was responsible for ∼50% of metabolism.


CYP2C9; [14C]lesinurad; absolute bioavailability; accelerated mass spectrometry (AMS); disposition; epoxide hydrolase; human

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