Single and multiple-dose pharmacokinetics of tepoxalin and its active metabolite after oral administration to rabbits (Oryctolagus cuniculus)
2008
POLLOCK, C.G. | CARPENTER, J.W. | KOCH, D.E. | HUNTER, R.P.
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. Cmax of the parent compound was reached between 3 and 8 h of drug administration, with a harmonic mean t₁/₂ of 3.6 h. Peak tepoxalin plasma concentrations were 207 ± 49 ng/mL. After oral administration, the metabolite RWJ 20142 achieved Cmax in plasma 2-8 h after administration, with a t₁/₂ 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.
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