Etoricoxib is a potent selective COX-2 inhibitor in man. Ex vivo whole-blood assays assessed COX-2 inhibition after oral administration of etoricoxib in single (5-500 mg) and multiple (25-150 mg) once-daily doses to healthy human subjects. A separate study examined ex vivo gastric mucosal PGE2 synthesis after etoricoxib (120 mg qd), naproxen (500 mg bid), or placebo for 5 days. The effect of etoricoxib 120 mg qd on the COX-1-mediated antiplatelet effects of low-dose aspirin (ASA) was also assessed. The mean (time)-weighted average inhibition (WAI) of lipopolysaccharide (LPS)-stimulated PGE2 (COX-2 assay) vcrsus placebo was dose related after single (range: 3.1%-99.1%) and multiple doses (range: 52.5%-96.7%). PGE2 remained significantly inhibited 24 hours postdose at steady state. Inhibition of LPS-stimulated PGE2 showed a strong relationship with etoricoxib plasma concentrations; ex vivo, IC50 was almost identical to in vitro. Multiple dosing of etoricoxib (up to 150 mg qd) showed no important effects on serum TXB2, bleeding time, or platelet aggregation (COX-1-mediated effects). The nonselective nonsteroidal anti-inflammatory (NSAID) naproxen significantly inhibited (approximately 78%) ex vivo prostaglandin synthesis in gastric mucosa; etoricoxib had no effect. Etoricoxib did not interfere with the antiplatelet effects of low-dose ASA, as assessed by serum TXB2 and platelet aggregation. Etoricoxib was generally well tolerated, even at doses above the clinical dose range. Based on these results, etoricoxib is a potent selective inhibitor of COX-2 after single and multiple dosing regimens and does not inhibit prostaglandin synthesis in the gastric mucosa, even at doses above the clinical dose range of 60 to 120 mg.
Etoricoxib is a potent selective COX-2 inhibitor in man. Ex vivo whole-blood assays assessed COX-2 inhibition after oral administration of etoricoxib in single (5-500 mg) and multiple (25-150 mg) once-daily doses to healthy human subjects. A separate study examined ex vivo gastric mucosal PGE2 synthesis after etoricoxib (120 mg qd), naproxen (500 mg bid), or placebo for 5 days. The effect of etoricoxib 120 mg qd on the COX-1-mediated antiplatelet effects of low-dose aspirin (ASA) was also assessed. The mean (time)-weighted average inhibition (WAI) of lipopolysaccharide (LPS)-stimulated PGE2 (COX-2 assay) vcrsus placebo was dose related after single (range: 3.1%-99.1%) and multiple doses (range: 52.5%-96.7%). PGE2 remained significantly inhibited 24 hours postdose at steady state. Inhibition of LPS-stimulated PGE2 showed a strong relationship with etoricoxib plasma concentrations; ex vivo, IC50 was almost identical to in vitro. Multiple dosing of etoricoxib (up to 150 mg qd) showed no important effects on serum TXB2, bleeding time, or platelet aggregation (COX-1-mediated effects). The nonselective nonsteroidal anti-inflammatory (NSAID) naproxen significantly inhibited (approximately 78%) ex vivo prostaglandin synthesis in gastric mucosa; etoricoxib had no effect. Etoricoxib did not interfere with the antiplatelet effects of low-dose ASA, as assessed by serum TXB2 and platelet aggregation. Etoricoxib was generally well tolerated, even at doses above the clinical dose range. Based on these results, etoricoxib is a potent selective inhibitor of COX-2 after single and multiple dosing regimens and does not inhibit prostaglandin synthesis in the gastric mucosa, even at doses above the clinical dose range of 60 to 120 mg.
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