title: Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal-salt diet.
abstract: BACKGROUND
  This study compared directly the renal effects of two selective cyclooxygenase (COX)-2 inhibitors (rofecoxib and celecoxib) with naproxen (dual COX-1/COX-2 inhibitor) and placebo in healthy elderly subjects on a sodium-replete diet.
  
  
  METHODS
  A total of 67 elderly subjects stabilized in the clinic for weight and urinary sodium on a controlled 200-mEq sodium diet were randomized in a double-blind fashion to receive rofecoxib, 25 mg daily (n = 17); celecoxib, 200 mg twice daily (n = 17); naproxen, 500 mg twice daily (n = 17); or matching placebo (n = 16) for 28 days. Subjects were sequestered in the clinic for the first 14 treatment days on the controlled diet.
  
  
  RESULTS
  Daily urinary sodium excretion during the first 72 hours of treatment (primary endpoint) significantly decreased in rofecoxib, celecoxib, and naproxen groups compared with baseline (P < or =.05). Rofecoxib and celecoxib decreases in urinary sodium excretion rates that were comparable with each other, on the basis of predefined boundaries (-39.5 versus -27.1 mEq/d, respectively) and to naproxen (-40.6, mEq/d). Rofecoxib, celecoxib, and naproxen increased mean systolic blood pressure to a similar degree (3.4, 4.3, and 3.1 mm Hg, respectively, versus -1.3 mm Hg for placebo) after 14 days of treatment; small changes also occurred in diastolic blood pressure (0.3, 0.8, and -0.4 mm Hg, respectively, versus -1.4 mm Hg for placebo). Changes from baseline in creatinine clearance, body weight, and urinary potassium excretion among active treatments were similar. After 28 days of treatment, findings were generally consistent with those at 14 days. No subject reported edema or discontinued treatment as the result of an adverse experience.
  
  
  CONCLUSIONS
  In healthy elderly subjects on a sodium-replete diet, the COX-2 inhibitors rofecoxib and celecoxib did not differ from a nonselective nonsteroidal anti-inflammatory drug (naproxen), in influencing renal function as measured by urinary sodium excretion, systolic and diastolic blood pressure, creatinine clearance, or weight change.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065, USA. jules_schwartz@meck.com
authors.forename: J I
authors.initials: JI
authors.lastname: Schwartz
authors.forename: K
authors.initials: K
authors.lastname: Vandormael
authors.forename: M P
authors.initials: MP
authors.lastname: Malice
authors.forename: R N
authors.initials: RN
authors.lastname: Kalyani
authors.forename: K C
authors.initials: KC
authors.lastname: Lasseter
authors.forename: G B
authors.initials: GB
authors.lastname: Holmes
authors.forename: B J
authors.initials: BJ
authors.lastname: Gertz
authors.forename: K M
authors.initials: KM
authors.lastname: Gottesdiener
authors.forename: M
authors.initials: M
authors.lastname: Laurenzi
authors.forename: K-J
authors.initials: KJ
authors.lastname: Redfern
authors.forename: K
authors.initials: K
authors.lastname: Brune
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D000068579:Celecoxib; D003404:Creatinine / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004032:Diet; D004311:Double-Blind Method; D004573:Electrolytes / Q000097:blood; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007783:Lactones / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects*; D011188:Potassium / Q000652:urine; D011720:Pyrazoles; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides / Q000009:adverse effects*; D013450:Sulfones
chemical_list: D016861:Cyclooxygenase Inhibitors; D004573:Electrolytes; D007783:Lactones; D011720:Pyrazoles; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; D012964:Sodium; D003404:Creatinine; D000068579:Celecoxib; D011188:Potassium