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Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal-salt diet
J I Schwartz1, K Vandormael, M P Malice
1Merck Research Laboratories, Rahway, NJ 07065, USA. jules_schwartz@meck.com
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.
Conclusion:
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.
Insights
Selective COX-2 inhibitors rofecoxib and celecoxib, and naproxen, similarly affected renal function in healthy elderly individuals. These drugs did not differ in their impact on urinary sodium excretion, blood pressure, or weight.
Area of Science:
- Nephrology
- Pharmacology
- Geriatrics
Background:
- The renal effects of selective cyclooxygenase-2 (COX-2) inhibitors are not fully understood, particularly in comparison to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs).
- Elderly individuals may be more susceptible to the renal side effects of NSAIDs.
Purpose of the Study:
- To directly compare the renal effects of two selective COX-2 inhibitors, rofecoxib and celecoxib, with a dual COX-1/COX-2 inhibitor, naproxen, and placebo.
- To evaluate these effects in healthy elderly subjects on a sodium-replete diet.
Main Methods:
- A double-blind, randomized study involving 67 healthy elderly subjects.
- Subjects received rofecoxib (25 mg/day), celecoxib (200 mg twice daily), naproxen (500 mg twice daily), or placebo for 28 days.
- Subjects were on a controlled 200-mEq sodium diet and sequestered for the first 14 days.
Main Results:
- All active treatments (rofecoxib, celecoxib, naproxen) significantly decreased urinary sodium excretion in the first 72 hours compared to baseline.
- The reduction in urinary sodium excretion was comparable between rofecoxib, celecoxib, and naproxen.
- Rofecoxib, celecoxib, and naproxen similarly increased systolic and diastolic blood pressure compared to placebo.
- No significant differences were observed in changes in creatinine clearance, body weight, or urinary potassium excretion among the active treatment groups.
Conclusions:
- In healthy elderly individuals on a sodium-replete diet, selective COX-2 inhibitors (rofecoxib, celecoxib) did not exhibit different renal effects compared to naproxen.
- These findings suggest similar impacts on renal function, including urinary sodium excretion and blood pressure, across these NSAIDs in this population.
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