Effect of losartan and furosemide on the urinary excretion of oxypurinol and uric acid.

Abstract

Losartan potassium (losartan) is an angiotensin II receptor antagonist used for the treatment of hypertension1, which opposes the action of angiotensin II at the AT1 receptor. Losartan has a uricosuric action, which depends on the inhibition of uric acid reabsorption in the proximal tubules2. On the other hand, furosemide is diuretic and is used for the treatment of heart failure, hypertension and edema. It inhibits the absorption of chloride and sodium at Henle’s loop, resulting in an increase in the rate of urine formation together with natriuresis. Further, it increases the concentration of serum uric acid, which is attributable to a furosemide-induced decrease in extracellular fluid and the urinary excretion of uric acid. Many previous studies 5-7 have demonstrated that glucagon, amino acids, benzbromarone, and probenecid increase the urinary excretion of oxypurinol and uric acid, suggesting that latter share a renal transport pathway. With these findings in mind, we speculated that losartan may increase the urinary excretion of oxypurinol, while furosemide may have the opposite effect causing its urinary excretion to decrease. Oxypurinol is a metabolite of allopurinol, which is used for the treatment of hyperuricemia. Although both allopurinol and oxypurinol are potent inhibitors of xanthine oxidase, the biological half time of oxypurinol is longer than that of allopurinol. Accordingly, the