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

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 mu g .h/m lfollowing i. v. and p. o. administration, respectively. Elimination half-lives (t1/2 beta) 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 AUC(0-24h)/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 beta g/ml. Furthermore, higher doses of sarafloxacin are required to minimize antimicrobial resistance considering the MPC theory.