Background: This study focused on utilizing pharmacokinetics/pharmacodynamics (PK/PD) modeling to optimize\ntherapeutic dosage regimens of sarafloxacin against avian pathogenic Escherichia. coli O78 strain in Muscovy ducks.\nThe ex vivo PK/PD study of sarafloxacin was conducted in Muscovy ducks after intravenous (i.v.) and oral (p.o.)\nadministrations at a single dose of 10 mg/kg bodyweight (BW). The serum samples were analyzed by reverse phase\nhigh-performance liquid chromatography (RP-HPLC) using a fluorescence detection method. Sarafloxacin PK data\nwere analyzed by a non-compartmental method using Winnonlin software.\nResults: Calculations of the area under the concentration-time curves (AUC0-24h) were 8.57 �± 0.59 and 8.37 �± 0.29 �¼g �· h/ml\nfollowing i.v. and p.o. administration, respectively. Elimination half-lives (t1/2�²) were 6.11 �± 0.99 h and 8.21 �± 0.64 h\nfor i.v. injection and p.o. administration, respectively. The mean in vitro plasma protein binding of sarafloxacin\nwas 39.3%. Integration using the sigmoid Emax model, the mean values of AUC0-24h/MIC needed for bacteriostatic,\nbactericidal and bacterial eradication action were 25.4, 40.6, and 94.4 h, respectively.\nConclusions: Sarafloxacin administered at a 10 mg/kg dose may be insufficient for treatment of E. coli O78\ninfections with an MIC equally to or over 0.125 �¼g/ml. Furthermore, higher doses of sarafloxacin are required to\nminimize antimicrobial resistance considering the MPC theory.
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