Pharmacokinetic and pharmacodynamic modeling of sarafloxacin against avian pathogenic Escherichia coli in Muscovy ducks

Abstract

Background: This study focused on utilizing pharmacokinetics/pharmacodynamics (PK/PD) modeling to optimize therapeutic dosage regimens of sarafloxacin against avian pathogenic Escherichia. coli O78 strain in Muscovy ducks. The ex vivo PK/PD study of sarafloxacin was conducted in Muscovy ducks after intravenous (i.v.) and oral (p.o.) administrations at a single dose of 10 mg/kg bodyweight (BW). The serum samples were analyzed by reverse phase high-performance liquid chromatography (RP-HPLC) using a fluorescence detection method. Sarafloxacin PK data were analyzed by a non-compartmental method using Winnonlin software. Results: Calculations of the area under the concentration-time curves (AUC0-24h) were 8.57 ± 0.59 and 8.37 ± 0.29 μg · h/ml following i.v. and p.o. administration, respectively. Elimination half-lives (t 1/2β) were 6.11 ± 0.99 h and 8.21 ± 0.64 h for i.v. injection and p.o. administration, respectively. The mean in vitro plasma protein binding of sarafloxacin was 39.3%. Integration using the sigmoid E max model, the mean values of AUC0-24h/MIC needed for bacteriostatic, bactericidal and bacterial eradication action were 25.4, 40.6, and 94.4 h, respectively. Conclusions: Sarafloxacin administered at a 10 mg/kg dose may be insufficient for treatment of E. coli O78 infections with an MIC equally to or over 0.125 μg/ml. Furthermore, higher doses of sarafloxacin are required to minimize antimicrobial resistance considering the MPC theory.