Effect of fenofibrate on uric acid metabolism and urate transporter 1.
OBJECTIVE
To examine the effects of fenofibrate, an antilipotropic drug, on uric acid metabolism in healthy male subjects and on urate transporter 1 (URAT1).


METHODS
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.


RESULTS
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.


CONCLUSIONS
Fenofibrate decreased serum uric acid levels by increasing its urinary excretion, most likely through the inhibition of URAT1 by fenofibric acid, its major metabolite.
Uetake
Daijiro
D
Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo. uetake@jikei.ac.jp
Ohno
Iwao
I
Ichida
Kimiyoshi
K
Yamaguchi
Yuichiro
Y
Saikawa
Hajime
H
Endou
Hitoshi
H
Hosoya
Tatsuo
T
D000328:Adult; D002460:Cell Line; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D008297:Male; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine
D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014527:Uric Acid; D011345:Fenofibrate