Animal welfare and theraphy in the horse: comparison of age-related pharmacokinetic of naproxen

Naproxene (10 mg/kg b.w.) was administered i.v. once (single trial) and per os every 24 hours for day 0 through 4 (multiple trial). Blood samples were collected before, then periodically after naproxene administration. Concentration of naproxene in plasma samples was determined by use of high-performance liquid chromatography. Mean concentration of naproxene in serum 5 minutes after single administration was 79.68±5.56 µg/ml. Serum naproxene concentration decreased in a curvilinear fashion, beeing 2.12± 1.16 µg/ml at 24 hours after administration, last sample time. No significant differences were noticed concerning the pharmacokinetic pattern between treated horses. After multiple administration, no accumulation of drug occurred, as seen in the single treatment. Twenty-four hours after each administrations serum concentrations of the a.i. were always between 3 and 5 µg/ml, and no variations of the concentrations detected 3 h after each treatment have been noticed. Pharmacokinetic variables were estimated. After i.v. single administration, the plasma concentration versus time data could best described by a two-exponential equation for all horses. Median naproxene AUC was 360.06 h*µg/ml, median plasma clearance was 28.99 ml/hr/kg, median steady-state volume of distribution was 227.03 ml/kg and median terminal half-life was 6.42 hours. After oral multiple administration (first day), the plasma concentration versus time data could best described by a mono-exponential equation for all horses. Naproxene peack concentrations between 28.83 and 57.19 µg/ml (mean Cmax: 41.14 µg/ml) have been reached 1.21-1.95 hours post-administration (mean Tmax: 1.62 h). Median naproxene AUC was 449.46 hr*µg/ml, median plasma clearance was 24.68 ml/hr/kg and median terminal half-life was 6.31 hours. Protein binding of naproxene, determined by ultrafiltration at concentrations of 1, 5, 10 15, 20, 50, 100 and µg/ml, was about 99%.