Effect of rofecoxib, etoricoxib, celecoxib, and naproxen on urinary excretion of prostanoids in elderly volunteers

Abstract

Purpose COX-2 inhibitors (COX2i) and nonselective NSAIDs affect systemic and renal prostaglandin synthesis and may have differential effects on vasoactive eicosanoids [prostacyclin, PGI2; thromboxane, TxB]. This study evaluated the effects of placebo (P), an NSAID [naproxen (N) 500 mg BID], and 3 COX2i [rofecoxib (R) 25 mg QD, etoricoxib (E) 90 mg QD, and celecoxib (C) 200 mg BID] on urinary prostanoids, 11-dehydro TxB2 (TxB-M; systemic TxB production measure), and 2,3 dinor 6-keto PGF1α, (PGI-M; systemic PGI2 production measure). Methods 152 patients (ages 60 to 85 yr) in 2 randomized, double-blind, placebo-controlled, 2-week parallel trials had prostanoids assayed from 8-hr urinary collections at pretreatment and Day 15. Results Effects were consistent for C, N, and P in both studies, so data for the 3 groups were pooled across trials. Results are below: (See Table) Conclusions COX-2 inhibitors had similar but partial reductions (p<0.89) in PGI2 synthesis [significantly less than that caused by naproxen (p<0.05)]. COX-2 inhibitors had no meaningful effect on systemic thromboxane [naproxen caused a substantial reduction (p<0.05) consistent with its effects on ex vivo serum TXB2 production and platelet aggregation]. Clinical Pharmacology & Therapeutics (2004) 75, P34–P34; doi: 10.1016/j.clpt.2003.11.127 Table 1. % Change from baseline in Urinary Excretion of Prostanoids (Mean SE) Treatment N PGI-M N TxB-M Rofecoxib 17 −58.9±4.6 17 −16.9±8.0 Etoricoxib 20 −58.3±4.4 21 0.9±8.9 Celecoxib 38 −58.2±2.9 38 −3.7±5.8 Naproxen 38 −75.1±1.7 38 −84.5±0.9 Placebo 37 −9.1±6.5 38 7.2±6.5