Renal effects of selective cyclooxygenase-2 inhibition in normotensive salt-depleted subjects

Purpose: TO compare the renal hemodynamic and tubular effects of celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) to those of naproxen, a nonselective inhibitor of cyclooxygenases in salt-depleted subjects. Methods and subjects: Forty subjects were randomized into four parallel gro ups to receive 200 mg celecoxib twice a day, 400 mg celecoxib twice a day, 500 mg naproxen twice a day, or a placebo for 7 days according to a double- blind study design. Blood pressure, renal hemodynamics, and urinary water a nd electrolyte excretion were measured before and for 3 hours after drug in take on days 1 and 7, Results: Celecoxib had no effect on systemic blood pressure, but short-term transient decreases in renal blood flow and glomerular filtration rate wer e found with the highest dose of 400 mg on day 1, On the first day, both ce lecoxib and naproxen decreased urine output (P < .05) and sodium, lithium, and potassium excretion (P < .01). On day 7, similar effects on water and s odium excretion were observed, During repeated administration, a significan t sodium retention occurred during the first 3 days. Conclusion: In salt-depleted subjects, selective inhibition of COX-2 causes sodium and potassium retention. This suggests that an increased selectivit y for COX-2 does not spare the kidney, at least during salt depletion.