Sulindac reduces the urinary excretion of prostaglandins and impairs renal function in cirrhosis with ascites.
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 F1 alpha (6-keto-PGF1 alpha) 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 less than 0.05), 6-keto-PGF1 alpha (from 19.9 +/- 2.9 to 5.6 +/- 1.1 ng/h; p less than 0.02) GFR (from 111 +/- 15 to 67 +/- 10 ml/min; p less than 0.01) and CH2O (from 7 +/- 1.5 to 3.7 +/- 1.3 ml/min; p less than 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.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine*; D001201:Ascites / Q000503:physiopathology; D001834:Body Water / Q000378:metabolism; D015232:Dinoprostone; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007700:Kinetics; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D009638:Norepinephrine / Q000097:blood; D011458:Prostaglandins E / Q000652:urine*; D012083:Renin / Q000097:blood; D013467:Sulindac / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood
D007192:Indenes; D011458:Prostaglandins E; D014667:Vasopressins; D013467:Sulindac; D015121:6-Ketoprostaglandin F1 alpha; D012083:Renin; D015232:Dinoprostone; D009638:Norepinephrine