Sulindac does not spare renal prostaglandins.
It has been suggested that the nonsteroidal anti-inflammatory drug, sulindac, selectively spares renal prostaglandin synthesis. We compared the effect of placebo and sulindac 300 mg daily for one week on furosemide-stimulated renal prostaglandin synthesis in twelve healthy young men. Sulindac reduced serum thromboxane B2, a measure of platelet thromboxane A2 production, from 21 +/- 3.9 to 10.9 +/- 2.2 ng/ml (p less than 0.01) but had no effect on body weight, blood pressure or serum creatinine. Sulindac did, however, decrease the natriuretic effect of intravenous furosemide, and reduced the increment in plasma renin activity. The excretion rates of 6-keto-prostaglandin F1 alpha and thromboxane B2 in urine were reduced by 34 and 27% respectively (p less than 0.001 for both). The reduced excretion rate was particularly prominent in the first ten minutes after furosemide injection. While these decreases are less marked than those seen with indomethacin, the reduction in platelet thromboxane A2 production is also of lesser degree. We conclude that, in the dose used, sulindac is a less potent inhibitor of cyclo-oxygenase than indomethacin and has no selective renal sparing effect.
Waslen
T A
TA
Department of Pharmacology, University of Saskatchewan, Saskatoon.
McCauley
F A
FA
Wilson
T W
TW
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000652:urine; D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D005665:Furosemide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011188:Potassium / Q000097:blood; D012016:Reference Values; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood; D013467:Sulindac / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood / Q000652:urine
D007192:Indenes; D013467:Sulindac; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D005665:Furosemide; D012964:Sodium; D003404:Creatinine; D012083:Renin; D011188:Potassium