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Renal effects of cyclooxygenase inhibitors in volume-depleted dogs

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image of Inflammopharmacology

Objective: The objective of this study was to investigate the renal effects of celecoxib, a cyclooxygenase-2 (COX-2) specific nonsteroidal anti-inflammatory drug (NSAID).Subjects and treatment: Six volume-depleted, conscious, chronically instrumented dogs received four treatments using a cross-over design, with at least 13 days between treatments. An i.v. bolus dose (3, 10, and 30 mol/kg) of vehicle, indomethacin, celecoxib, or 6-MNA, the active metabolite of nabumetone, were administered with an hour between doses.Methods: Renal function was assessed at baseline and 30 min after each dose.Results: Treatment with indomethacin or celecoxib resulted in a dose-dependent reduction in renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow, sodium excretion, and fractional sodium excretion. GFR was reduced by 27% with 30 mol/kg indomethacin (p < 0.05) and by 58% with 30 mol/kg celecoxib (p < 0.5). Similarly, RPF was significantly (p < 0.05) reduced by 33% and 65% with 30 mol/kg indomethacin and celecoxib, respectively. Reductions in renal function with celecoxib occurred at a therapeutic index (determined by comparison anti-edemic activities of the drugs in rat paw carrageenan assays) equal to or lower than indomethacin. In contrast, treatment with vehicle or 6-MNA resulted in no reductions in renal function.Conclusion: Administration of either celecoxib (specific COX-2 inhibitor) or indomethacin (selective COX-1 inhibitor) resulted in significant reductions in renal function. COX-2 specific inhibitors do not appear to lack the renal effects of NSAIDs.


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