The effect of misoprostol on indomethacin-induced renal dysfunction in well-compensated cirrhosis.
OBJECTIVE
Indomethacin has been shown to have adverse effects on renal function in patients with well-compensated alcoholic cirrhosis. The aim of this study was to determine whether an oral prostaglandin E1 analogue, misoprostol, could prevent this indomethacin-induced renal dysfunction.


METHODS
Six patients with well-compensated alcoholic cirrhosis were studied. Renal hemodynamics and tubular function were assessed by clearance techniques before and after an oral dose of (i) 50 mg of indomethacin alone (I50), and (ii) a combination of I50 and 200 micrograms of misoprostol.


RESULTS
I50 produced a significant reduction in glomerular filtration rate, a fall in effective renal plasma flow and an increase in renal vascular resistance. Two hundred micrograms of misoprostol was able to abolish the deleterious renal effects of indomethacin totally, yielding an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance as well as an increase in urinary volume and urinary sodium excretion. These beneficial effects were maximal in the hour immediately following medication, but were only transient, and this may be a limiting factor in its clinical use.


CONCLUSIONS
If the beneficial renal effects of misoprostol could be confirmed after chronic administration, then the vasodilatory, natriuretic and diuretic potential of 200 micrograms of misoprostol could be of potential therapeutic value in patients with well-compensated alcoholic cirrhosis who require non-steroidal anti-inflammatory drug therapy.
Department of Gastroenterology, Alfred Hospital, Prahran, Victoria, Australia.
F
F
Wong
D
D
Massie
P
P
Hsu
F
F
Dudley
D000284:Administration, Oral; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000008:administration & dosage / Q000494:pharmacology*; D011465:Prostaglandins, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011465:Prostaglandins, Synthetic; D016595:Misoprostol; D012964:Sodium; D007213:Indomethacin