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

Abstract

1. The objectives of this study were to determine the absolute bioavailability of lesinurad and to characterized its disposition in humans.

2. 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%.

3. The disposition of lesinurad in humans involves hepatic oxidation and renal elimination following administration of oral [¹⁴C]lesinurad dose.

4. 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.

5. In vitro metabolism studies identified CYP2C9 as the predominant isoform, and summation of metabolites indicated that it was responsible for ∼50% of metabolism.

Keywords:

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

Disclosure statement

No potential conflict of interest was reported by the authors.