title: Pharmacokinetics/pharmacodynamics of marbofloxacin in a Pasteurella multocida serious murine lung infection model.
abstract: BACKGROUND
  Marbofloxacin is a third-generation fluoroquinolone developed solely for veterinary medicine with a broad spectrum of antibacterial activity against some Gram-positive and most Gram-negative bacteria, including the bovine respiratory tract pathogen, Pasteurella multocida. The objective of our study was to elucidate the pharmacokinetics and pharmacodynamics of marbofloxacin in a Pasteurella multocida infected murine lung model, and to estimate the magnitudes of pharmacokinetics-pharmacodynamics parameters associated with various effects.
  
  
  RESULTS
  The pharmacokinetic studies revealed marbofloxacin kinetics in infected mice were linear over a dose ranging from 1.25 to 10 mg/kg of body weight. The protein binding in the plasma of neutropenic infected mice was 29.77 %. The magnitudes of the ratio of the free-drug area under the concentration-time curve over 24 h to MIC (fAUC 0-24h/MIC) associated with static effect, a 2 log10 reduction and a 3 log10 reduction of bacterial counts were 40.84, 139.34, and 278.08 h, respectively.
  
  
  CONCLUSIONS
  Based on the dose range study, marbofloxacin exhibited concentration-dependent killing and the fAUC/MIC was the PK/PD index that correlated best with efficacy (R(2) = 83 %). On the basis of a bactericidal effect goal of fAUC 0-24h/MIC of 278.08 h, if marbofloxacin is used for the treatment of P. multocida serious lung infection with an MIC90 of 0.12 μg/ml, the current dose (2 mg/kg) would fail to achieve a bactericidal effect. It would benefit from higher doses (4 ~ 6 mg/kg) than those commonly used in clinical practice.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agriculture University, Guangzhou, China. 952605105@qq.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agriculture University, Guangzhou, China. 744952971@qq.com.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agriculture University, Guangzhou, China. 290806342@qq.com.
authors.forename: Changfu
authors.initials: C
authors.lastname: Cao
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agriculture University, Guangzhou, China. 1259756354@qq.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agriculture University, Guangzhou, China. 798551409@qq.com.
authors.forename: Meizhen
authors.initials: M
authors.lastname: Sun
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agriculture University, Guangzhou, China. 771879032@qq.com.
authors.forename: Chaoping
authors.initials: C
authors.lastname: Liang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agriculture University, Guangzhou, China. zlzeng@scau.edu.cn.
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009503:Neutropenia; D010326:Pasteurella Infections / Q000188:drug therapy / Q000382:microbiology*; D016979:Pasteurella multocida / Q000187:drug effects*; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C080260:marbofloxacin