Sulindac Reduces the Urinary Excretion of Prostaglandins and Impairs Renal Function in Cirrhosis with Ascites

Abstract

In 5 patients with cirrhosis and ascites the glomerular filtration rate (GFR), free water clearance (CH₂O) and urinary excretion of prostaglandin E₂ (PGE₂) and 6-keto-prostaglandin F_1α (6-keto-PGF_1α) were measured before and after a 3-day treatment with sulindac (400 mg/day). The administration of sulindac induced a marked fall of urinary excretion of PGE₂ (from 24.2 ± 5.5 to 3.8 ± 1.1 ng/h; p < 0.05), 6-keto-PGF_1α (from 19.9 ± 2.9 to 5.6 ± 1.1 ng/h; p < 0.02) GFR (from 111 ± 15 to 67 ± 10 ml/min; p < 0.01) and CH₂O (from 7 ± 1.5 to 3.7 ± 1.3 ml/min; p < 0.02) in all patients studied. The plasma concentration of the active metabolite sulindac sulfide in cirrhotics was 400% of that found in 6 healthy volunteers (9.6 ± 1.7 vs. 2.4 ± 0.6 ng/ml). Our results indicate that sulindac, at a dose of 400 mg/day, inhibits the renal synthesis of prostaglandins and impairs renal function in cirrhotics with ascites. These effects are probably related to the marked alteration of sulindac kinetics that occurs in these patients.