Effect of Fenofibrate on Uric Acid Metabolism and Urate Transporter 1

Abstract

To examine the effects of fenofibrate, an antilipotropic drug, on uric acid metabolism in healthy male subjects and on urate transporter 1 (URAT1). Fenofibrate was administered to nine male volunteers at a dose of 300 mg (corresponding to 200 mg of micronized fenofibrate), and the metabolic parameters of uric acid were investigated for more than 12 hours. In addition, the effect of fenofibrate on URAT1-expressing cells was examined. After the administration of fenofibrate, the concentration of serum uric acid had significantly decreased from 5.8+/-0.4 mg/dL to 4.3+/-0.3 mg/dL at 10 h. Uric acid clearance and the fractional excretion of uric acid increased. Fenofibric acid, a fenofibrate metabolite, inhibited URAT1 to an extent similar to that observed with benzbromarone and losartan. Fenofibrate decreased serum uric acid levels by increasing its urinary excretion, most likely through the inhibition of URAT1 by fenofibric acid, its major metabolite.