PK/PD modelling of enrofloxacin against Glaesserella parasuis infection in pigs.

Abstract

A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to optimize the dosing regimen of enrofloxacin (EN) against Glaesserella parasuis in pigs. EN (2.5mg/kg) was administered intramuscularly to eight healthy pigs and eight pigs that were experimentally infected with G.parasuis SW124. Blood samples were collected at predetermined time points. Plasma EN concentrations were determined, and the main PK parameters were estimated. The PD of EN against G.parasuis SW124 was also investigated in vitro and ex vivo. The dynamic behaviour of EN in pigs was consistent with a one-compartment model. Significant differences were observed between healthy and infected pigs in the area under the curve (AUC) (3.58±0.94 and 5.39±1.01μgh/ml, respectively) and the systemic clearance (CL) (736.32±171.46 and 479.36±96.81ml/h/kg, respectively), suggesting that the pathogenicity of G.parasuis SW124 to pigs might alter the PK profile of EN, and therefore should be considered in dose optimization. Both the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 0.125μg/ml in tryptone soya broth (TSB) medium or plasma. The mutant prevention concentration (MPC) was 0.6μg/ml. EN inhibited or killed G. parasuis SW124 in a concentration-dependent manner. The targeted endpoints of AUC24h /MIC for bacteriostasis, bactericidal action, and eradication were 5.10, 7.34, and 8.65h and 5.91, 9.01, and 10.90h in healthy and infected pigs, respectively. The optimal doses were 3.58-6.08mg/kg in healthy pigs and 2.71-4.99mg/kg in infected pigs from the point of view of preventing drug resistance.