In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration

Xiao, Xia; Lin, Pei; Jiang, Lijie; Lan, Weixuan; Xiao, Jiayu; Jiang, Yon-Jia; Wang, Zhiqiang

doi:10.3389/fphar.2018.00391

Cited by 9 publications

(12 citation statements)

References 35 publications

(48 reference statements)

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“…The initial bacteria concentration is crucial for time-killing curves. Identical conclusions have also been found in work by Xiao et al (2018c) .…”

Section: Discussionsupporting

confidence: 87%

“…It has been reported that a rational antibacterial dosage regimen based on pharmacokinetic and pharmacodynamic (PK/PD) modeling (especially in vivo ) could maximize the therapeutic effect and minimize the emergence of resistance ( Li et al, 2017 ; Xiao et al, 2018c ). To achieve this aim, several PK/PD studies of florfenicol have been undertaken.…”

Section: Introductionmentioning

confidence: 99%

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In vivo Pharmacokinetic and Pharmacodynamic (PK/PD) Modeling and Establishment of the PK/PD Cutoff of Florfenicol Against Pasteurella multocida in Ducks

et al. 2021

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Pasteurella multocida can invade and translocate through endothelial cells and result in vascular-system infection, which can cause severe economic losses in the poultry industry. Antibacterial therapy (especially florfenicol) plays an important part in controlling P. multocida infection. To preserve the effect of florfenicol, in vivo pharmacokinetic/pharmacodynamic (PK/PD) modeling of florfenicol against three P. multocida strains in duck was established. Then, the efficacy of the currently marketed dose, a rational dosage regimen for populations, and the PK/PD cutoff were predicted through Monte Carlo simulations (MCSs). The area under the concentration–time curve from 0 to 24 h/minimum inhibitory concentration (AUC0–24 h/MIC) was the optimal PK/PD parameter. The PK/PD surrogate values of florfenicol against P. multocida were similar using different organs as the PD target, but varied in different strains. For the florfenicol-sensitive strain 0825Y1, when the AUC0–24 h/MIC reached 117.54 and 108.19, florfenicol showed a bactericidal effect in the liver and lung, respectively. For the florfenicol-sensitive strain 0901J1, the corresponding value was 78.39 and 54.30, respectively. For the florfenicol-resistant strain JY160110, florfenicol could attain a maximum effect of 1 – log10 reduction in bacteria in the liver and lung when the AUC0–24 h/MIC reached 2.03 and 2.06, respectively. The PK/PD-based prediction for the population dose indicated a poor effect for the low end of the currently marketed dose (40 mg/kg body weight per day), but a robust effect for the high end of the currently marketed dose (60 mg/kg body weight per day) with a target attainment rate of 92.79% and 81.44% against P. multocida in mainland China and worldwide, respectively. The recommended dose optimized by MCSs was 52 mg/kg body weight in mainland China. The PK/PD cutoff of florfenicol against P. multocida at the low end and high end of the current daily dose (40 and 60 mg/kg body weight) and predicted daily dose in mainland China (52 mg/kg body weight) was 0.25, 4, and 0.5 μg/ml, respectively. These results suggested that more than one strain should be involved for PK/PD modeling and contributed to rational use of florfenicol in populations. We also provided fundamental data for determination of florfenicol breakpoints in poultry.

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“…The initial bacteria concentration is crucial for time-killing curves. Identical conclusions have also been found in work by Xiao et al (2018c) .…”

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

In vivo Pharmacokinetic and Pharmacodynamic (PK/PD) Modeling and Establishment of the PK/PD Cutoff of Florfenicol Against Pasteurella multocida in Ducks

et al. 2021

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“…This phenomenon was also observed in our previous study. The AUC 0–24 /MIC values of danofloxacin against Salmonella typhimurium for the same effect in different organs also showed marked differences [ 22 ]. Similar results were also reported in other studies [ 20 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, for PK/PD modeling of enrofloxacin, it is important to involve its metabolism to ciprofloxacin in the modeling. According to our previous study, the selection of the target organ for PD determination is critical for parameter magnitude calculation in antimicrobial PK/PD modeling [ 22 ]. Whether this is true for enrofloxacin requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

In vivo pharmacokinetic/Pharmacodynamic modeling of Enrofloxacin against Escherichia coli in broiler chickens

et al. 2018

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BackgroundSystemic Escherichia coli infections cause early mortality of commercial broiler chickens. Although enrofloxacin has long been used in poultry, the in vivo pharmacokinetic/pharmacodynamic (PK/PD) relationship of enrofloxacin against E. coli is unclear. The present study aimed to establish an in vivo PK/PD model of enrofloxacin against E. coli in seven-day-old chicks and to ascertain whether the selection of target organ for PD determination is critical for parameter magnitude calculation in enrofloxacin PK/PD modeling.ResultsThe in vivo effectiveness of enrofloxacin against E. coli in different organs varied, with the Emax ranging from − 4.4 to − 5.8 Log10 colony forming units (cfu)/mL or cfu/g. Both the surrogate AUC0–24/MIC of enrofloxacin or AUC0–24/MIC of the combination of enrofloxacin and ciprofloxacin correlated well with effectiveness in each organ. The AUC0–24/MIC ratio of the combination of enrofloxacin and ciprofloxacin producing bactericidal and elimination effects were 21.29 and 32.13 in blood; 41.68, and 58.52 in the liver; and 27.65 and 46.22 in the lung, respectively.ConclusionsThe in vivo effectiveness of enrofloxacin against E. coli in different organs was not identical after administration of the same dosage. To describe the magnitude of PK/PD parameter exactly, bacterial loading reduction in different organs as PD endpoints should be evaluated and compared in PK/PD modeling. The selection of a target organ to evaluate PDs is critical for rational dosage recommendation.

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“…Dosage regimens vary depending on the types of drugs, animals, and bacteria. For example, the optimized dose regimens for danofloxacin against M. haemolytica in calves was 0.738 mg/kg administered by a single intravenous (IV) bolus, while against S. typhimurium in rabbits the regimen was daily oral administration of 10 mg/kg for 3 days, and against E. coli in camels was 4 mg/kg by intramuscular administration [314546]. Moreover, the same drug can have a different dosing regimen against the same bacterial infection in different animals.…”

Section: Formation Of a Dosage Regimen Via Pk/pd Modelsmentioning

confidence: 99%

Pharmacokinetics/Pharmacodynamics models of veterinary antimicrobial agents

Luo

Chen

et al. 2019

J Vet Sci

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Misuse and abuse of veterinary antimicrobial agents have led to an alarming increase in bacterial resistance, clinical treatment failure, and drug residues. To address these problems, consistent and appropriate dosage regimens for veterinary antimicrobial agents are needed. Pharmacokinetics/Pharmacodynamics (PK/PD) models have been widely used to establish rational dosage regimens for veterinary antimicrobial agents that can achieve effective prevention and treatment of bacterial diseases and avoid the development of bacterial resistance. This review introduces building methods for PK/PD models and describes current PK/PD research progress toward rational dosage regimens for veterinary antimicrobial agents. Finally, the challenges and prospects of PK/PD models in the design of dosage regimens for veterinary antimicrobial agents are reviewed. This review will help to increase awareness of PK/PD modeling among veterinarians and hopefully promote its development and future use.

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In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration

Cited by 9 publications

References 35 publications

In vivo Pharmacokinetic and Pharmacodynamic (PK/PD) Modeling and Establishment of the PK/PD Cutoff of Florfenicol Against Pasteurella multocida in Ducks

In vivo Pharmacokinetic and Pharmacodynamic (PK/PD) Modeling and Establishment of the PK/PD Cutoff of Florfenicol Against Pasteurella multocida in Ducks

In vivo pharmacokinetic/Pharmacodynamic modeling of Enrofloxacin against Escherichia coli in broiler chickens

Pharmacokinetics/Pharmacodynamics models of veterinary antimicrobial agents

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