Pharmacokinetics of vitacoxib in rabbits after intravenous and oral administration.

This study describes the pharmacokinetics of vitacoxib in healthy rabbits following administration of 10 mg/kg intravenous (i.v.) and 10 mg/kg oral. Twelve New Zealand white rabbits were randomly allocated to two equally sized treatment groups. Blood samples were collected at predetermined times from 0 to 36 hr after treatment. Plasma drug concentrations were determined using UPLC-MS/MS. Pharmacokinetic analysis was completed using noncompartmental methods via WinNonlin((TM)) 6.4 software. The mean concentration area under curve (AUC(last)) for vitacoxib was determined to be 11.0 +/- 4.37 mu g hr/ml for i.v. administration and 2.82 +/- 0.98 mu g hr/ml for oral administration. The elimination half-life (T-1/2 lambda z) was 6.30 +/- 2.44 and 6.30 +/- 1.19 hr for the i.v. and oral route, respectively. The C-max (maximum plasma concentration) and T-max (time to reach the observed maximum (peak) concentration at steady-state) following oral application were 189 +/- 83.1 ng/ml and 6.58 +/- 3.41 hr, respectively. Mean residence time (MRTlast) following i.v. injection was 6.91 +/- 3.22 and 11.7 +/- 2.12 hr after oral administration. The mean bioavailability of oral administration was calculated to be 25.6%. No adverse effects were observed in any rabbit. Further studies characterizing the pharmacodynamics of vitacoxib are required to develop a formulation of vitacoxib for rabbits.