Pharmacokinetics/pharmacodynamics of marbofloxacin in a Pasteurella multocida serious murine lung infection model

作者：Qu, Ying; Qiu, Zhenzhen; Cao, Changfu; Lu, Yan; Sun, Meizhen; Liang, Chaoping; Zeng, Zhenling^*

来源：BMC Veterinary Research, 2015, 11(1): 294.

DOI：10.1186/s12917-015-0608-1

• Marbofloxacin
• Pharmacokinetics/Pharmacodynamics
• Pasteurella multocida
• Mouse-lung model

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 log(10) reduction and a 3 log(10) 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 mu g/ml, the current dose (2 mg/kg) would fail to achieve a bactericidal effect. It would benefit from higher doses (4 similar to 6 mg/kg) than those commonly used in clinical practice.

• 出版日期2015-12-2
• 单位华南农业大学