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Should we take advantage of their uricosuric properties in clinical practice?
The interesting study published in this issue of the journal by Takahashi et al sheds light on two drugs, losartan and fenofibrate, which have hypouricaemic properties, in addition to their main therapeutic effects.1
Losartan potassium is an orally active angiotensin II receptor antagonist used for the treatment of hypertension. This product and its long life metabolite E-3174 are potent antagonists at the AT1 receptor. The observation that losartan increases urinary uric acid excretion and reduces serum uric acid level was first made in a pilot study conducted in healthy subjects and published in 1992. Uric acid fractional clearance was mainly increased during the first four hours after drug intake in a time course consistent with a direct effect of the drug. The increase was found to be dose dependent and to persist after seven days of administration.2 Angiotensin is known to lower uric acid renal clearance,3 but the uricosuric effect of losartan did not appear to be mediated by angiotensin inhibition: in one study, infusion of E-3174, the active metabolite of losartan, did not modify uric acid excretion, although it efficiently decreased blood pressure.4 The early and transient uricosuric action of losartan was therefore attributed mainly to the mother compound. Further suggestions of an effect independent of angiotensin II receptor blockade came from the observation that the uricosuric effect did not vary with a sodium diet5 and was not seen with other angiotensin II receptor antagonists.6–8
“Losartan and E-3174 target the urate anion exchanger URAT1”
Losartan and its metabolite E-3174 …