Effect of losartan potassium, an angiotensin II receptor antagonist, on renal excretion of oxypurinol and purine bases.
OBJECTIVE
To examine whether losartan affects the plasma concentrations and urinary excretion of purine bases and oxypurinol.


METHODS
We administered allopurinol (300 mg) and then 9 h later losartan potassium (100 mg) to 5 healthy subjects.


RESULTS
The urinary excretion of uric acid increased by 3.9- and 2.6-fold, and that of oxypurinol by 2- and 1.8-fold, at 1 to 2 h and at 2 to 3 h, respectively, after administration of losartan potassium. The fractional clearance of uric acid was increased by 4.3- and 3.2-fold, oxypurinol by 2.3- and 2.1-fold, and xanthine by 1.32- and 1.26-fold, at 1 to 2 h and at 2 to 3 h, respectively, after administration of losartan potassium. The plasma concentrations of uric acid decreased by 8% and 16%, oxypurinol by 7% and 11%, and xanthine by 42% and 45%, at 1.5 and 2.5 h, respectively, after oral administration.


CONCLUSIONS
These results suggest that losartan potassium could increase urinary excretion of uric acid, xanthine, and oxypurinol by acting on their common renal transport pathways, since it was found that uric acid may share a renal transport pathway with oxypurinol and xanthine. It is also suggested that the effect of losartan potassium on oxypurinol and uric acid is clinically important, since the hypouricemic effect of a combination therapy using allopurinol and losartan potassium may be less than additive, while the uricosuric effect of losartan potassium may increase the frequency of calculi in the urinary tract.
Yamamoto
T
T
Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Moriwaki
Y
Y
Takahashi
S
S
Tsutsumi
Z
Z
Hada
T
T
D000328:Adult; D000493:Allopurinol / Q000378:metabolism / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D003404:Creatinine / Q000097:blood / Q000652:urine; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D019808:Losartan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D010117:Oxypurinol / Q000097:blood / Q000652:urine*; D011687:Purines / Q000097:blood / Q000652:urine*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D014970:Xanthines / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D011687:Purines; D014970:Xanthines; D000493:Allopurinol; D003404:Creatinine; D012083:Renin; D010117:Oxypurinol; D019808:Losartan