Effect of nonsteroidal anti-inflammatory drugs with varying extent of COX-2-COX-1 selectivity on urinary sodium and potassium excretion in the rat.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have different selectivity to inhibit cyclooxygenase-1 (COX-1) and COX-2. Treatment with NSAIDs has been associated with kidney side effects. We compared the effect of a selected group of NSAIDs with different COX-2--COX-1 selectivities on urinary sodium and potassium excretion in rats. Each treatment with rofecoxib, celecoxib, meloxicam, diclofenac, and flurbiprofen (30, 120, 9, 30, and 125 mg/kg, respectively) and placebo was administered orally once daily for 4 days. Urine was collected 0-8 h after each dose. Urinary sodium and potassium excretion and urine flow rate were compared with placebo. As compared with placebo, rofecoxib, celecoxib, diclofenac, and flurbiprofen significantly reduced excretion rate of sodium (rofecoxib, 0.28 +/- 0.02 vs. 0.41 +/- 0.03; celecoxib, 0.23 +/- 0.03 vs. 0.48 +/- 0.04; diclofenac, 0.09 +/- 0.02 vs. 0.46 +/- 0.03; and flurbiprofen, 0.11 +/- 0.02 vs. 0.47 +/- 0.02 micromol/(min x 100 g)) and potassium (rofecoxib, 0.55 +/- 0.04 vs. 0.68 +/- 0.04; celecoxib, 0.50 +/- 0.06 vs. 0.72 +/- 0.06; diclofenac, 0.26 +/- 0.05 vs. 0.67 +/- 0.04; and flurbiprofen, 0.35 +/- 0.05 vs. 0.62 +/- 0.03 micromol/ (min x 100 g)). Rofecoxib and flurbiprofen significantly reduced urine flow rate. Meloxicam had no significant effect on either sodium and potassium excretion or on the urine flow rate. At the examined dosage level, no relationship was found between reported COX-2--COX-1 selectivity and urinary electrolytes excretion.
Harirforoosh
Sam
S
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
Jamali
Fakhreddin
F
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D008297:Male; D008565:Membrane Proteins; D011188:Potassium / Q000652:urine*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine*; D014563:Urodynamics / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D012964:Sodium; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D011188:Potassium