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

Clin Pharmacol Ther. 1999 Jul;66(1):76-84. doi: 10.1016/S0009-9236(99)70056-1.

Abstract

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 groups 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 and electrolyte excretion were measured before and for 3 hours after drug intake 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 were found with the highest dose of 400 mg on day 1. On the first day, both celecoxib and naproxen decreased urine output (P < .05) and sodium, lithium, and potassium excretion (P < .01). On day 7, similar effects on water and sodium excretion were observed. During repeated administration, a significant 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 selectivity for COX-2 does not spare the kidney, at least during salt depletion.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure
  • Celecoxib
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Double-Blind Method
  • Humans
  • Isoenzymes / drug effects*
  • Kidney / drug effects*
  • Kidney / metabolism*
  • Lithium / blood
  • Lithium / urine
  • Male
  • Membrane Proteins
  • Naproxen / pharmacology
  • Potassium / blood
  • Potassium / urine
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Pyrazoles
  • Reference Values
  • Sodium / blood*
  • Sodium / urine
  • Sulfonamides / pharmacology*
  • Volunteers

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Pyrazoles
  • Sulfonamides
  • Naproxen
  • Lithium
  • Sodium
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib
  • Potassium