Pharmacokinetics and ex vivo pharmacodynamics of cefquinome in porcine serum and tissue cage fluids

Abstract

A tissue cage (TC) model was used to evaluate the pharmacokinetics and ex vivo pharmacodynamics of cefquinome after intravenous (IV) and intramuscular (IM) administration to piglets at 2 mg/kg bodyweight. The mean values of area under the concentration-time curve (AUC) were 21.28 (IV) and 21.37 (IM) μg h/mL for serum, and 17.40 (IV) and 16.57 (IM) μg h/mL for TC fluid (TCF), respectively. Values of maximum concentration (C(max)) were 6.15 μg/mL (serum) and 1.15 μg/mL (TCF) after IM administration. The elimination half-lives (t(1/2β)) in TCF (10.63 h IV and 11.81 h IM) were significantly higher than those in serum (2.33 h IV and 2.30 h IM) (P<0.05). The values of AUC(TCF)/AUC(serum) (%) after IV and IM administration were 82.4% and 80.7%, respectively. The ex vivo time-kill curves were established for serum and TCF samples using Escherichia coli ATCC 25922. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values of cefquinome against E. coli were 0.030 and 0.060 μg/mL in Mueller-Hinton broth, and 0.032 and 0.064 μg/mL in both serum and TCF, respectively. The ex vivo growth inhibition data of TCF after IM administration were fitted to the sigmoid E(max) model; AUC(24h)/MIC was 35.01 h for bactericidal activity and 44.28 h for virtual eradication, respectively. The findings from this study suggest that cefquinome may be therapeutically effective in diseases of pigs caused by E. coli when used at a dose rate of 1.33 mg/kg administered every 24 h for organisms with MIC90⩽0.50 μg/mL.

Keywords: Cefquinome; Escherichia coli; Ex vivo; Piglets; Tissue cage fluids.