Effect of the angiotensin II receptor antagonist losartan on uric acid and oxypurine metabolism in healthy subjects.
OBJECTIVE
The acute effects of the angiotensin II receptor antagonist losartan on uric acid and oxypurine metabolism were evaluated.


METHODS
Losartan (50 mg) was administered orally to 6 healthy males. Blood and urine samples for uric acid and oxypurine were collected before and up to 6 hours after losartan administration. The same examinations were performed later using enalapril (5 mg).


RESULTS
Losartan decreased the serum uric acid concentration (from 5.9 +/- 0.9 to 5.2 +/- 1.0 mg/dl) and increased its fractional clearance, which reached a maximum after 2 hours, while enalapril did not. Losartan also induced an increase in the plasma concentration of hypoxanthine, peaking in the fourth hour, and a decrease in its urinary clearance, while the plasma xanthine concentration and its urinary clearance were unchanged. The extent of uric acid excretion was much greater than that of the oxypurines.


CONCLUSIONS
Losartan, which has a high affinity for the urate/anion exchanger, has a transient uricosuric effect. Our data indicate that losartan induces a significant decrease in the urinary excretion of hypoxanthine without changes in xanthine.
Hamada
Toshihiro
T
Department of Cardiovascular Medicine, Tottori University Hospital, Yonago.
Hisatome
Ichiro
I
Kinugasa
Yoshiharu
Y
Matsubara
Koichi
K
Shimizu
Hideki
H
Tanaka
Hiroaki
H
Furuse
Masako
M
Sonoyama
Kazuhiko
K
Yamamoto
Yasutaka
Y
Ohtahara
Akira
A
Igawa
Osamu
O
Shigemasa
Chiaki
C
Yamamoto
Tetsuya
T
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology; D006801:Humans; D019271:Hypoxanthine / Q000652:urine; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D010117:Oxypurinol / Q000652:urine*; D014527:Uric Acid / Q000097:blood*; D019820:Xanthine / Q000652:urine
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D004656:Enalapril; D010117:Oxypurinol; D019808:Losartan