Absorption, metabolism, and excretion of etoricoxib, a potent and selective cyclooxygenase-2 inhibitor, in healthy male volunteers

Abstract

[14C]Etoricoxib (100 μCi/dose) was administered to six healthy male subjects (i.v., 25 mg; p.o., 100 mg). Following the i.v. dose, the plasma clearance was 57 ml/min, and the harmonic mean half-life was 24.8 h. Etoricoxib accounted for the majority of the radioactivity (∼75%) present in plasma following both i.v. and p.o. doses. The oral dose, administered as a solution in polyethylene glycol-400, was well absorbed (absolute bioavailability of ∼83%). Total recovery of radioactivity in the excreta was 90% (i.v.) and 80% (p.o.), with 70% (i.v.) and 60% (p.o.) excreted in urine and 20% in feces after either route of administration. Radiochromatographic analysis of the excreta revealed that etoricoxib was metabolized extensively, and only a minor fraction of the dose (<1%) was excreted unchanged. Radiochromatograms of urine and feces showed that the 6′-carboxylic acid derivative of etoricoxib was the major metabolite observed (≥65% of the total radioactivity). 6′-Hydroxymethyl-etoricoxib and etoricoxib-1′-N-oxide, as well as the O-β-D-glucuronide conjugate and the 1′-N-oxide derivative of 6′-hydroxymethyl-etoricoxib, were present in the excreta also (individually, ≤10% of the total radioactivity). In healthy male subjects, therefore, etoricoxib is well absorbed, is metabolized extensively via oxidation (6′-methyl oxidation ∼1′-N-oxidation), and the metabolites are excreted largely in the urine.