Abstract
The aim of this study was to evaluate the effect of diclofenac on the disposition and renal clearance of amoxicillin. In this cross over study with a 1 week washout period, 10 ewes received amoxicillin intravenously (10 mg/kg body mass) alone or plus diclofenac sodium (2.5 mg/kg b.m.), given intramuscularly 30 minutes prior to amoxicillin administration. Concentrations of amoxicillin in plasma and urine were measured using high performance liquid chromatography (HPLC) with fluorescence detection. Concomitant administration of diclofenac with amoxicillin resulted in no significant alterations in the pharmacokinetic parameters or renal elimination for amoxicillin following intravenous administration. Intravenous administration of amoxicillin alone or concomitant with diclofenac resulted in mean +/- SD elimination half-life (t(1/2 beta)), of 0.79 +/- 0.11 h versus 0.8 +/- 0.09 h, mean residence time (MRT) of 0.8 +/- 0.15 h versus 0.9 +/- 0.17 h, total body clearance (CLB) of 0.25 +/- 0.02 L/h/kg vs 0.24 +/- 0.04 L/h/kg and area under the curves (AUC) of 35.2 +/- 6.2 mu g/h/mL vs 39.5 +/- 5.7 mu g/h/mL, respectively. Amoxicillin was eliminated unchanged via the urine, with renal clearance (CIR of 0.24 +/- 0.05 L/h/kg and 0.27 +/- 0.07 L/h/kg in the animal given amoxicillin alone or concomitant with diclofenac, respectively. Concurrent administration of diclofenac had no significant effect on the single-dose pharmacokinetics or renal elimination of amoxicillin given intravenously in ewes.