Sulindac does not spare renal prostaglandins

Area of Science:

• Pharmacology
• Nephrology
• Prostaglandin Biology

Background:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) can affect kidney function.
• Sulindac has been suggested to selectively spare renal prostaglandin synthesis.
• Prostaglandins play a role in regulating renal blood flow and sodium excretion.

Purpose of the Study:

• To compare the effects of sulindac and placebo on furosemide-stimulated renal prostaglandin synthesis in healthy men.
• To determine if sulindac has a selective renal-sparing effect on prostaglandin synthesis.

Main Methods:

• Twelve healthy young men received either placebo or sulindac (300 mg daily) for one week.
• Furosemide was administered intravenously to stimulate renal prostaglandin synthesis.
• Measurements included serum thromboxane B2, urinary 6-keto-prostaglandin F1 alpha and thromboxane B2 excretion, blood pressure, body weight, and serum creatinine.

Main Results:

• Sulindac significantly reduced serum thromboxane B2 (platelet thromboxane A2 production).
• Urinary excretion rates of 6-keto-prostaglandin F1 alpha and thromboxane B2 were significantly reduced by sulindac.
• Sulindac decreased the natriuretic effect of furosemide and reduced the increment in plasma renin activity.
• No significant effects on body weight, blood pressure, or serum creatinine were observed.

Conclusions:

• Sulindac, at the dose used, is a less potent inhibitor of cyclo-oxygenase compared to indomethacin.
• Sulindac does not demonstrate a selective renal-sparing effect on prostaglandin synthesis.
• The observed reductions in renal prostaglandin metabolites suggest a systemic effect of sulindac on prostaglandin production.