The anti-inflammatory agent, tepoxalin, was administered to eight healthy 6-month-old female New Zealand white rabbits once daily at an oral dose of 10 mg/kg. Blood samples were obtained immediately before and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 h postadministration on days 1 and 10. Tepoxalin and its active metabolite, RWJ 20142, concentrations were determined in plasma by use of high-performance liquid chromatography with mass spectrometry. C(max) of the parent compound was reached between 3 and 8 h of drug administration, with a harmonic mean t(1/2) of 3.6 h. Peak tepoxalin plasma concentrations were 207 +/- 49 ng/mL. After oral administration, the metabolite RWJ 20142 achieved C(max) in plasma 2-8 h after administration, with a t(1/2) of 1.9-4.8 h (harmonic mean 2.8 h). Peak plasma concentrations of RWJ 20142 on day 1 were 2551 +/- 1034 ng/mL.