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In vitro Dynamic Pharmacokinetic/Pharmacodynamic (PK/PD) study and COPD of Marbofloxacin against Haemophilus parasuis.

Sun J, Xiao X, Huang RJ, Yang T, Chen Y, Fang X, Huang T, Zhou YF, Liu YH - BMC Vet. Res. (2015)

Bottom Line: The PK/PD surrogate markers Cmax/MIC, Cmax/MPC (the maximum concentration divided by MIC or mutant prevention concentration (MPC)) and AUC 24h/MIC, AUC 24h/MPC (the area under the curve during the first 24 h divided by MIC or MPC) simulated the antimicrobial effect of marbofloxacin successfully with the R(2) of 0.9928 and 0.9911, respectively.The target values of 3-log10-unit and 4-log10-unit reduction for AUC 24h/MPC were 33 and 42, while the same efficacy for AUC 24h/MIC were 88 and 110.The PK/PD surrogate markers AUC 24h/MIC, Cmax/MIC and AUC 24h/MPC, Cmax/MPC properly described the effects of marbofloxacin.

View Article: PubMed Central - PubMed

Affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. jiansun@scau.edu.cn.

ABSTRACT

Background: Haemophilus parasuis (H. parasuis) can invade the body and cause systemic infection under stress conditions. Marbofloxacin has been recommended for the treatment of swine infections. However, few studies have investigated the PK/PD characteristics and PK/PD cutoff (COPD) of this drug against H. parasuis.

Results: MICs of marbofloxacin against 198 H. parasuis isolates were determined. The MIC50 and MIC90 were 2 and 8 mg/L, respectively. An in vitro dynamic PK/PD model was established to study the PK/PD relationship of marbofloxacin against H. parasuis. The PK/PD surrogate markers Cmax/MIC, Cmax/MPC (the maximum concentration divided by MIC or mutant prevention concentration (MPC)) and AUC 24h/MIC, AUC 24h/MPC (the area under the curve during the first 24 h divided by MIC or MPC) simulated the antimicrobial effect of marbofloxacin successfully with the R(2) of 0.9928 and 0.9911, respectively. The target values of 3-log10-unit and 4-log10-unit reduction for AUC 24h/MPC were 33 and 42, while the same efficacy for AUC 24h/MIC were 88 and 110. The COPD deduced from Monte Carlo simulation (MCS) for marbofloxacin against H. parasuis was 0.5 mg/L. The recommended dose of marbofloxacin against H. parasuis with MIC ≤ 2 mg/L was 16 mg/kg body weight (BW).

Conclusions: The PK/PD surrogate markers AUC 24h/MIC, Cmax/MIC and AUC 24h/MPC, Cmax/MPC properly described the effects of marbofloxacin. Marbofloxacin can achieve the best efficacy at dosage of 16 mg/kg BW for strains with MIC values ≤ 2 mg/L, therefore, it is obligatory to know the sensitivity of the pathogen and to treat animals as early as possible. The very first COPD provide fundamental data for marbofloxacin breakpoint determination.

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The Probability of target attainment (PTA) for different marbofloxacin doses against isolates of H. parasuis with different MICs
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Fig5: The Probability of target attainment (PTA) for different marbofloxacin doses against isolates of H. parasuis with different MICs

Mentions: As there are no PK data of marbofloxacin with a dose of 2 mg/kg BW, data of 2.5 mg/kg BW were used for MCS. In the simulation, with the PK/PD target AUC24h/MIC of 88, PTA > 90 % could only be achieved for isolates with MIC ≤ 0.125 mg/L (Fig. 5). For dosage regimen of 8 mg/kg BW with a single dose administered by IM, PTA > 90 % could be achieved for isolates with MIC ≤ 0.5 mg/L (Fig. 5). The COPD for marbofloxacin against H. parasuis was 0.5 mg/L. The recommended dose of marbofloxacin for bactericidal effect against H. parasuis was 16 mg/kg BW.Fig. 5


In vitro Dynamic Pharmacokinetic/Pharmacodynamic (PK/PD) study and COPD of Marbofloxacin against Haemophilus parasuis.

Sun J, Xiao X, Huang RJ, Yang T, Chen Y, Fang X, Huang T, Zhou YF, Liu YH - BMC Vet. Res. (2015)

The Probability of target attainment (PTA) for different marbofloxacin doses against isolates of H. parasuis with different MICs
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666160&req=5

Fig5: The Probability of target attainment (PTA) for different marbofloxacin doses against isolates of H. parasuis with different MICs
Mentions: As there are no PK data of marbofloxacin with a dose of 2 mg/kg BW, data of 2.5 mg/kg BW were used for MCS. In the simulation, with the PK/PD target AUC24h/MIC of 88, PTA > 90 % could only be achieved for isolates with MIC ≤ 0.125 mg/L (Fig. 5). For dosage regimen of 8 mg/kg BW with a single dose administered by IM, PTA > 90 % could be achieved for isolates with MIC ≤ 0.5 mg/L (Fig. 5). The COPD for marbofloxacin against H. parasuis was 0.5 mg/L. The recommended dose of marbofloxacin for bactericidal effect against H. parasuis was 16 mg/kg BW.Fig. 5

Bottom Line: The PK/PD surrogate markers Cmax/MIC, Cmax/MPC (the maximum concentration divided by MIC or mutant prevention concentration (MPC)) and AUC 24h/MIC, AUC 24h/MPC (the area under the curve during the first 24 h divided by MIC or MPC) simulated the antimicrobial effect of marbofloxacin successfully with the R(2) of 0.9928 and 0.9911, respectively.The target values of 3-log10-unit and 4-log10-unit reduction for AUC 24h/MPC were 33 and 42, while the same efficacy for AUC 24h/MIC were 88 and 110.The PK/PD surrogate markers AUC 24h/MIC, Cmax/MIC and AUC 24h/MPC, Cmax/MPC properly described the effects of marbofloxacin.

View Article: PubMed Central - PubMed

Affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. jiansun@scau.edu.cn.

ABSTRACT

Background: Haemophilus parasuis (H. parasuis) can invade the body and cause systemic infection under stress conditions. Marbofloxacin has been recommended for the treatment of swine infections. However, few studies have investigated the PK/PD characteristics and PK/PD cutoff (COPD) of this drug against H. parasuis.

Results: MICs of marbofloxacin against 198 H. parasuis isolates were determined. The MIC50 and MIC90 were 2 and 8 mg/L, respectively. An in vitro dynamic PK/PD model was established to study the PK/PD relationship of marbofloxacin against H. parasuis. The PK/PD surrogate markers Cmax/MIC, Cmax/MPC (the maximum concentration divided by MIC or mutant prevention concentration (MPC)) and AUC 24h/MIC, AUC 24h/MPC (the area under the curve during the first 24 h divided by MIC or MPC) simulated the antimicrobial effect of marbofloxacin successfully with the R(2) of 0.9928 and 0.9911, respectively. The target values of 3-log10-unit and 4-log10-unit reduction for AUC 24h/MPC were 33 and 42, while the same efficacy for AUC 24h/MIC were 88 and 110. The COPD deduced from Monte Carlo simulation (MCS) for marbofloxacin against H. parasuis was 0.5 mg/L. The recommended dose of marbofloxacin against H. parasuis with MIC ≤ 2 mg/L was 16 mg/kg body weight (BW).

Conclusions: The PK/PD surrogate markers AUC 24h/MIC, Cmax/MIC and AUC 24h/MPC, Cmax/MPC properly described the effects of marbofloxacin. Marbofloxacin can achieve the best efficacy at dosage of 16 mg/kg BW for strains with MIC values ≤ 2 mg/L, therefore, it is obligatory to know the sensitivity of the pathogen and to treat animals as early as possible. The very first COPD provide fundamental data for marbofloxacin breakpoint determination.

Show MeSH
Related in: MedlinePlus