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Ann Intern Med. 2000 Jul 4;133(1):1-9.

Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial.

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1
Division of Nephrology, Hennepin County Medical Center and Total Renal Research, Inc., Minneapolis, Minnesota 55415, USA.

Abstract

BACKGROUND:

Most nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 (COX-1), whose inhibition is associated with gastrointestinal ulceration, and COX-2, whose inhibition is associated with therapeutic benefits. Although agents that do not produce COX-1 activity may have fewer adverse effects, targeted disruption of the COX-2 allele in mice has resulted in severe renal problems, suggesting that COX-2 inhibition may also produce adverse effects.

OBJECTIVE:

To determine the effect of rofecoxib, a member of the coxib class of drugs and a specific inhibitor of the COX-2 enzyme, on renal function in elderly patients.

DESIGN:

A randomized, three-period, single-dose crossover study and a randomized, parallel-group, multiple-dose study.

SETTING:

Clinical research units.

PATIENTS:

75 patients 60 to 80 years of age.

INTERVENTION:

In the first study, single doses of rofecoxib, 250 mg (about 5-fold to 20-fold the recommended dose); indomethacin, 75 mg; and placebo were administered to 15 patients. In the second study, multiple doses of rofecoxib, 12.5 or 25 mg/d; indomethacin, 50 mg three times daily; or placebo were administered to 60 patients. Patients in both studies received a low-sodium diet

MEASUREMENTS:

Glomerular filtration rate, creatinine clearance, and urinary and serum sodium and potassium values.

RESULTS:

Compared with placebo, single doses of rofecoxib and indomethacin decreased the glomerular filtration rate by 0.23 m/s (P < 0.001) and 0.18 mL/s (P = 0.003), respectively. In contrast, respective decreases of 0.14, 0.13, and 0.10 mL/s were observed after multiple doses of rofecoxib, 12.5 mg/d (P = 0.019); rofecoxib, 25 mg (P = 0.029), and indomethacin (P = 0.086) were administered. Changes in creatinine clearance and serum and urinary sodium and potassium were less pronounced.

CONCLUSIONS:

The effects of COX-2 inhibition on renal function are similar to those observed with nonselective NSAIDs. Thus, COX-2 seems to play an important role in human renal function.

PMID:
10877734
[Indexed for MEDLINE]
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