title: Sulindac is not renal sparing in man.
abstract: 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 PGF2 alpha (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 concentration of indomethacin (1.9 +/- 0.4 microgram/ml) and sulindac sulfide (7.7 +/- 1.9 microgram/ml) were those associated with clinical efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005665:Furosemide / Q000037:antagonists & inhibitors; D005919:Glomerular Filtration Rate; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011188:Potassium / Q000652:urine; D011458:Prostaglandins E / Q000652:urine; D011460:Prostaglandins F / Q000652:urine; D011863:Radioimmunoassay; D011897:Random Allocation; D012964:Sodium / Q000652:urine; D013467:Sulindac / Q000097:blood / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D007192:Indenes; D011458:Prostaglandins E; D011460:Prostaglandins F; D013467:Sulindac; D013929:Thromboxane B2; D005665:Furosemide; D012964:Sodium; D011188:Potassium; D007213:Indomethacin