Sulindac and indomethacin suppress the diuretic action of furosemide in patients with cirrhosis and ascites: evidence that sulindac affects renal prostaglandins.
Nonsteroidal anti-inflammatory drugs (NSAID) suppress prostaglandin-dependent renal blood flow and furosemide-induced diuresis in patients with cirrhosis and ascites. Since sulindac may selectively spare inhibition of renal prostaglandins, we evaluated the interactions of acute administration of sulindac or indomethacin with furosemide in 15 patients with cirrhosis and ascites. Prior to furosemide, indomethacin reduced creatinine clearance (by 55%), urinary volume (by 82%), sodium (by 93%), and prostaglandin E2 (by 87%) (all P less than 0.05), whereas sulindac had no effect. However, both drugs reduced furosemide-induced diuresis. Indomethacin appeared slightly more potent in reducing the diuresis (55% v 38%), natriuresis (67% v 52%), and prostaglandin E2 (PGE2) release (81% v 74%). In a similar protocol in healthy subjects, furosemide-induced diuresis and natriuresis were also blunted by both drugs. Thus, under conditions of enhanced prostaglandin activity from furosemide, sulindac does affect renal function. These data suggest that renal function should be monitored in patients with cirrhosis and ascites who receive sulindac as well as other NSAID.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001201:Ascites / Q000188:drug therapy / Q000652:urine; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000652:urine; D015232:Dinoprostone; D004231:Diuresis / Q000187:drug effects; D004341:Drug Evaluation; D005665:Furosemide / Q000037:antagonists & inhibitors*; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D007213:Indomethacin / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000652:urine; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011458:Prostaglandins E / Q000652:urine; D012964:Sodium / Q000652:urine; D013467:Sulindac / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D007192:Indenes; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E; D013467:Sulindac; D005665:Furosemide; D012964:Sodium; D003404:Creatinine; D015232:Dinoprostone; D011188:Potassium; D007213:Indomethacin