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 2mg/kg bodyweight. The mean values of area under the concentration–time curve (AUC) were 21.28 (IV) and 21.37 (IM)μgh/mL for serum, and 17.40 (IV) and 16.57 (IM)μgh/mL for TC fluid (TCF), respectively. Values of maximum concentration (Cmax) were 6.15μg/mL (serum) and 1.15μg/mL (TCF) after IM administration. The elimination half-lives (t1/2β) in TCF (10.63h IV and 11.81h IM) were significantly higher than those in serum (2.33h IV and 2.30h IM) (P<0.05). The values of AUCTCF/AUCserum (%) 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 0.060μg/mL in Mueller–Hinton broth, and 0.032 and 0.064μg/mL in both serum and TCF, respectively. The ex vivo growth inhibition data of TCF after IM administration were fitted to the sigmoid Emax model; AUC24h/MIC was 35.01h for bactericidal activity and 44.28h 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 1.33mg/kg administered every 24h for organisms with MIC90⩽0.50μg/mL.