Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet: a randomized, controlled trial
SK Swan, DW Rudy, KC Lasseter, CF Ryan… - Annals of internal …, 2000 - acpjournals.org
SK Swan, DW Rudy, KC Lasseter, CF Ryan, KL Buechel, LJ Lambrecht, MB Pinto, SC Dilzer…
Annals of internal medicine, 2000•acpjournals.orgBackground: 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 …
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 …
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 mL/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.
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