The dose-dependent effect of misoprostol on indomethacin-induced renal dysfunction in well compensated cirrhosis.
Misoprostol (200 micrograms) has been shown to acutely counteract the indomethacin-induced renal dysfunction in well compensated cirrhotic patients. The aim of this study was to determine if the prophylactic value of misoprostol was dose-dependent. Parameters of renal hemodynamics and tubular sodium and water handling were assessed by clearance techniques in 26 well compensated cirrhotic patients before and after an oral combination of 50 mg of indomethacin and various doses of misoprostol. The 200-micrograms dose was able to totally abolish the deleterious renal effects of indomethacin, whereas the 800-micrograms dose resulted in significant worsening of renal hemodynamics and sodium retention. These changes were maximal in the hour immediately after medications and slowly returned toward base-line levels thereafter. These results suggest that the renal protective effects of misoprostol is dose-dependent. However, until this apparent ability of 200 micrograms of misoprostol to prevent the adverse effects of indomethacin on renal function is confirmed with chronic frequent dosing, it would be prudent to avoid nonsteroidal anti-inflammatory therapy in patients with cirrhosis.
Wong
F
F
Department of Gastroenterology, Alfred Hospital, Victoria, Australia.
Massie
D
D
Hsu
P
P
Dudley
F
F
D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects*; D008104:Liver Cirrhosis, Alcoholic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000008:administration & dosage* / Q000494:pharmacology; D017596:Renal Plasma Flow, Effective / Q000187:drug effects
D016595:Misoprostol; D007213:Indomethacin