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 μg · h/ml following i.v. and p.o. administration, respectively. Elimination half-lives (t1/2β) 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 Emaxmodel, 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.
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, China.|Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
Yang
Y
Yu
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, China.|Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
Yu Feng
YF
Zhou
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, China.|Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
Jian
J
Sun
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.|Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
Wei
W
Shi
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, China.|Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
Xiao Ping
XP
Liao
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. lyh@scau.edu.cn.|Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, China. lyh@scau.edu.cn.|Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China. lyh@scau.edu.cn.|College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues, South China Agricultural University, Guangzhou, 510642, China. lyh@scau.edu.cn.
Ya Hong
YH
Liu
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D019540:Area Under Curve; D001715:Bird Diseases / Q000188:drug therapy*; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004372:Ducks; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000662:veterinary*; D006207:Half-Life; D007275:Injections, Intravenous; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; C047224:sarafloxacin
Avian pathogenic Escherichia Coli; Dosage regimens; Muscovy ducks; Mutant prevention concentration; Pharmacokinetics/pharmacodynamics; Sarafloxacin