Integrated pharmacokinetic–Pharmacodynamic (PK/PD) model to evaluate the in vivo antimicrobial activity of Marbofloxacin against Pasteurella multocida in piglets

Zeng, Qing; Xian, Min; Su, Jia; Li, Xiao Hong; Xiong, Wen Guang; Lü, Yan; Zeng, Zhen

doi:10.1186/s12917-017-1099-z

Cited by 11 publications

(11 citation statements)

References 38 publications

(43 reference statements)

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“…To the best of our knowledge, there has been no in vivo PK/PD modeling study of enrofloxacin against E. coli in chicks. One of the best PK/PD parameter for fluoroquinolones is AUC 0–24 /MIC [ 34 – 36 ], and this study further confirmed this conclusion. Both the surrogate AUC 0–24 /MIC for enrofloxacin or the combination of enrofloxacin and ciprofloxacin correlated well with effectiveness in each organ.…”

Section: Discussionsupporting

confidence: 76%

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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Section: Discussionsupporting

confidence: 76%

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

et al. 2018

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“…These three indexes were highly correlated, making it important to have data from several different dosing regimens to be able to distinguish between them. According to the previously published study, it has been demonstrated that AUC/MIC could be regarded as the right and optimal PK-PD index for MBF ( Sidhu et al, 2010 ; Jian et al, 2015 ; Lei et al, 2017a ; Zeng et al, 2017 ). Therefore, the best PK-PD index of AUC/MIC was selected to use for proposing the optimal dose in this study.…”

Section: Resultsmentioning

confidence: 99%

“…The best PK-PD index for a certain drug-bacteria combination is determined by plotting the value of an efficacy endpoint (typically log10 CFU/ml after 24 h of treatment) versus the magnitude of each of the three PK-PD indices. It has been reported that AUC/MIC could be the right and optimal PK-PD index for MBF based on the previously published study ( Sidhu et al, 2010 ; Jian et al, 2015 ; Lei et al, 2017a ; Zeng et al, 2017 ). The best PK-PD index of AUC/MIC was selected to use in this study.…”

Section: Methodsmentioning

confidence: 94%

PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

et al. 2017

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Marbofloxacin is a fluoroquinolone antibiotic and highly effective treatment for respiratory diseases. Here we aimed to evaluate the ex vivo activity of marbofloxacin against Streptococcus suis in pig serum, as well as the optimal dosages scheme for avoiding the fluoroquinolone resistance development. A single dose of 8 mg/kg body weight (bw) was administrated orally to healthy pigs and serum samples were collected during the next 72 h. Serum marbofloxacin content was determined by high-performance liquid chromatography. We estimated the Cmax (6.28 μg/ml), AUC0-24 h (60.30 μg.h/ml), AUC0-∞ (88.94 μg.h/ml), T1/2ke, (12.48 h), Tmax (0.75 h) and Clb (0.104 L/h) of marbofloxacin in pigs, as well as the bioavailability of marbofloxacin (94.21%) after a single 8 mg/kg oral administration. We also determined the pharmacodynamic of marbofloxacin against 134 Streptococcus suis strains isolated from Chinese cities in TSB and serum. These isolated strains had a MIC90 of 1 μg/ml. HB2, a virulent, serotype 2 isolate of SS, was selected for having antibacterial activity in TSB and serum to marbofloxacin. We determined the minimum inhibitory concentration (MIC, 1 μg/ml in TSB, 2 μg/ml in serum), minimum bactericidal concentration (MBC, 4 μg/ml in TSB, 4 μg/ml in serum), and mutant prevention concentration (2.56 μg/ml in TSB) for marbofloxacin against Streptococcus suis (HB2). In serum, by inhibitory sigmoid Emax modeling, the AUC0-24h/MIC values for marbofloxacin against HB2 were 25.23 (bacteriostatic), 35.64 (bactericidal), and 39.71 (elimination) h. Based on Monte Carlo simulations, the predicted optimal oral doses of marbofloxacin curing Streptococcus suis were 5.88 (bacteriostatic), 8.34 (bactericidal), and 9.36 (elimination) mg/kg.bw for a 50% target attainment ratio, and 8.16 (bacteriostatic), 11.31 (bactericidal), and 12.35 (elimination) mg/kg.bw for a 90% target attainment ratio. The data presented here provides optimized dosage information for clinical use; however, these predicted dosages should also be validated in clinical practice.

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“…PK/PD models are a vital tool in the analysis of the relationship between the time course and antibacterial effects of veterinary antibacterial agents and, thus, in optimizing a therapy regimen. In order to identify the clinically relevant relationship between the dosage interval time and the effect of a drug, PK/PD modeling, an advanced approach to determining a suitable daily dose and dosage interval, may be used [3738]. Such models have been widely used to establish the dosage regimens of different antimicrobial agents including fluoroquinolones, β-lactam, amphenicols, tetracyclines, aminoglycosides, macrolides, colistin, and valnemulin.…”

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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Integrated pharmacokinetic–Pharmacodynamic (PK/PD) model to evaluate the in vivo antimicrobial activity of Marbofloxacin against Pasteurella multocida in piglets

Cited by 11 publications

References 38 publications

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

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

PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

Pharmacokinetics/Pharmacodynamics models of veterinary antimicrobial agents

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