Sulindac is not renal sparing in man

Autor: Douglas G Roberts, Gary O. Zerbe, John G. Gerber, Alan S Nies, John S. Barnes
Rok vydání: 1985
Předmět:
Zdroj: Clinical Pharmacology and Therapeutics. 38:258-265
ISSN: 1532-6535
0009-9236
DOI: 10.1038/clpt.1985.168
Popis: We investigated the claimed renal-sparing effect of the cyclooxygenase inhibitor sulindac. Fifteen normal women following a diet of 50 mEq salt a day were randomly assigned to 5 days of either placebo, sulindac, 200 mg b.i.d., or indomethacin, 25 mg q.i.d., after first serving as their own controls. Renal effects were assessed by the excretion rate of prostaglandin (PG) E2 (an index of renal PG synthesis), sodium balance, plasma renin activity (PRA), and the response to furosemide. Systemic effects were assessed by collagen-induced platelet aggregation and thromboxane B2 formation and by the urinary excretion of a systemically formed metabolite of PGF2α (PGF-M). Both sulindac and indomethacin resulted in a positive sodium balance and a reduction in 24-hour urinary PGE2 excretion (range −49% to −86%). Basal PRA was decreased by indomethacin only, but the increases in PRA and in urinary PGE2 excretion in response to furosemide were inhibited by both sulindac and indomethacin. Sulindac reduced the natriuresis induced by furosemide, and indomethacin reduced the rise in inulin clearance after furosemide. Thus the two nonsteroidal anti-inflammatory drugs had similar effects on the kidney. Indomethacin had a greater effect than sulindac on the inhibition of collagen-induced platelet aggregation and thromboxane synthesis and the two drugs had equivalent effects on the reduction of PGF-M excretion. Peak plasma drug concentrations of indomethacin (1.9 ± 0.4 µg/ml) and sulindac sulfide (7.7 ± 1.9 µg/ml) were those associated with clinical efficacy. We conclude that sulindac has renal effects qualitatively comparable to those of indomethacin. Therefore, caution should continue to be exercised with the use of sulindac, as with other nonsteroidal anti-inflammatory drugs, in clinical situations in which cyclooxygenase inhibitors have been associated with deterioration of renal function. Clinical Pharmacology and Therapeutics (1985) 38, 258–265; doi:10.1038/clpt.1985.168
Databáze: OpenAIRE
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