The effects of the addition of losartan on uric acid metabolism in patients receiving indapamide

Objective A number of adverse metabolic effects are associated with indapamide administration, including an increase in serum uric acid levels. It has been reported that losartan can significantly decrease serum uric acid levels. However, there are no data on the effects of combination therapy of losartan with indapamide on uric acid metabolism. Methods We studied 20 hypertensive patients in whom serum metabolic parameters, including uric acid levels in serum and urine, were studied before and after eight weeks of indapamide administration (2.5 mg once daily) as well as eight weeks after combination treatment with indapamide (2.5 mg once daily) and losartan (50 mg/day). Results Indapamide evoked a significant decrease in systolic and diastolic blood pressure from a mean value of 157±12 mmHg/96±10 mmHg to a mean value of 139±14 mmHg/92±5 mmHg (p<0.01 for both comparisons). However, a significant increase in serum uric acid levels was noticed after indapamide administration (from a mean value of 4.9±1.6 mg/dl to a mean value of 5.9±1.2 mg/dl, p<0.01), associated with a decrease in the fractional excretion of uric acid (from a mean value of 9±5% to a mean value of 7±5.5%, p<0.05). The addition of losartan caused a further decrease in blood pressure from a mean value of 139±14 mmHg/92±5 mmHg to a mean value of 120±15 mmHg/84±4 mmHg (p<0.01 for both comparisons). This was followed by a significant decrease in serum uric acid levels to 5±1.1 mg/dl (p<0.01) due to a substantial increase in fractional urate excretion (from 7±5.5 to 8.7±6%, p<0.05). Conclusion The addition of losartan could offset the hyperuricaemic effect of indapamide administration.

[1]  F. Coe,et al.  Safety of losartan in hypertensive patients with thiazide-induced hyperuricemia. , 1999, Kidney International.

[2]  M. Elisaf,et al.  Effectiveness and metabolic effects of perindopril and diuretics combination in primary hypertension , 1999, Journal of Human Hypertension.

[3]  M. Elisaf,et al.  Effect of micronized fenofibrate and losartan combination on uric acid metabolism in hypertensive patients with hyperuricemia. , 1999, Journal of cardiovascular pharmacology.

[4]  M. Burnier,et al.  Renal effects of angiotensin II receptor blockade in normotensive subjects. , 1996, Kidney international.

[5]  H. Trachtman Sodium and water homeostasis. , 1995, Pediatric clinics of North America.

[6]  B. Wiens,et al.  Effects of losartan on a background of hydrochlorothiazide in patients with hypertension. , 1995, Hypertension.

[7]  B Bornkessel,et al.  [Angiotensin II receptor antagonists]. , 1995, Medizinische Monatsschrift fur Pharmazeuten.

[8]  T. Rosenthal,et al.  Hemodynamic and humoral effects of the angiotensin II antagonist losartan in essential hypertension. , 1994, American journal of hypertension.

[9]  M. Burnier,et al.  Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects. , 1993, Hypertension.

[10]  P. Timmermans,et al.  Effects of DuP 753 on proximal nephron and renal transport. , 1991, American journal of hypertension.

[11]  K. Osei,et al.  Indapamide. Effects on apoprotein, lipoprotein, and glucoregulation in ambulatory diabetic patients. , 1986, Archives of internal medicine.

[12]  L. Ruilope,et al.  Controlled trial of losartan given concomitantly with different doses of hydrochlorothiazide in hypertensive patients. , 1996, Blood pressure.

[13]  R. Edwards,et al.  Interaction of nonpeptide angiotensin II receptor antagonists with the urate transporter in rat renal brush-border membranes. , 1996, The Journal of pharmacology and experimental therapeutics.

[14]  Y. Imai,et al.  Hypotensive effect of losartan, a nonpeptide angiotensin II receptor antagonist, in essential hypertension. , 1993, American journal of hypertension.

[15]  R. Moore,et al.  The pharmacology and clinical pharmacology of indapamide. , 1981, Postgraduate medical journal.

[16]  Moore Ra,et al.  The pharmacology and clinical pharmacology of indapamide. , 1981 .