Fig. 2

Effects of lesinurad on urate handling and lesinurad pharmacokinetics in healthy human volunteers. a Dose-dependent increase in fractional excretion of uric acid (FE _UA ) after a single 200-mg, 400-mg, or 600-mg dose of lesinurad. FE_UA was elevated from baseline (–18 to 0 hours) at 0–6 hours after dosing and then returned to normal after 24 hours. For all doses, p < 0.001 at 0–6 hours and 6–12 hours relative to baseline. b FE_UA levels increased with increasing plasma lesinurad. The half-maximal effective concentration of plasma lesinurad concentrations on FE_UA was 13 μM. Results are from healthy volunteers on a single 200-mg, 400-mg, or 600-mg dose of lesinurad. c Healthy volunteers on a single 200-mg, 400-mg, or 600-mg dose of lesinurad had a dose-dependent decrease in serum uric acid (sUA), for every drug treatment point for all doses relative to baseline, p <0.001. d Urinary excretion of lesinurad correlated linearly with plasma lesinurad following a single dose of 200, 400, or 600 mg lesinurad. AUC area under the curve for plasma concentration vs. time