Lung microdialysis study of florfenicol in pigs after single intramuscular administration

Yang, Bo; Gao, Jindong; Cao, Xingyuan; Wang, Q. Y.; Sun, Guozi; Yang, J. J.

doi:10.1111/jvp.12387

Cited by 9 publications

(10 citation statements)

References 28 publications

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“…The normalized sensitivity coefficient (NSC), which was used to identify the relative importance of each model parameter, was calculated as previously described (Campbell, ). Data sets used for parameter estimation and sensitivity analysis were from previously published pharmacokinetics studies (Liu et al., ; Yang, Gao, Cao, Wang, & Yang, ). All mathematical operations during the development of the PBPK model were performed using acslXtreme software.…”

Section: Methodsmentioning

confidence: 99%

“…The model was validated by comparing model predictions with the experimental data. Data sets for model validation were from the literature (EMEA, ; Geng, Li, Tian, Liu, & Yu, ; Jiang et al., ; Li, ; Voorspoels et al., ; Yang et al., ). It should be noted that there were two different sets of concentration–time data in the study by Yang et al., and these data sets demonstrated the concentration–time courses of unbound FF in porcine lung interstitial fluid following a single intramuscular administration at two different doses (20 and 50 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

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Diffusion‐limited PBPK model for predicting pulmonary pharmacokinetics of florfenicol in pig

Qian

Wang

Yang

et al. 2017

Vet Pharm & Therapeutics

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For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been thought to be responsible for antimicrobial efficacy. In this study, a diffusion-limited physiologically based pharmacokinetic (PBPK) model was developed to predict the pulmonary pharmacokinetics of florfenicol (FF) in pigs. The model included separate compartments corresponding to blood, diffusion-limited lung, flow-limited muscle, liver, and kidney and an extra compartment representing the remaining carcass. The absorption rate constant and renal and hepatic clearance of FF were determined in vivo. Other parameters were taken from the literature or optimized based on existing pharmacokinetic data. All mathematical operations during the development of the model were performed using acslXtreme version 3.0.2.1 (Aegis Technologies Group, Inc., Huntsville, AL, USA). The model accurately predicted the concentration-time courses of FF in lung interstitial fluid, serum, and plasma following different dosing schedules, except at the dose of 15 mg/kg. When compared with the tissue residue data, the model generally underestimated the FF concentration at the injection site, whereas it gave good predictions of FF concentrations in lung, liver, and kidney at early time points. The model predictions provide a scientific basis for the dosage regimen design of FF.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Diffusion‐limited PBPK model for predicting pulmonary pharmacokinetics of florfenicol in pig

Qian

Wang

Yang

et al. 2017

Vet Pharm & Therapeutics

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“…It is a powerful technology that can facilitate the development of drugs. This technique has been used to explore drug pharmacokinetics in several species, such as pigs (Tyvold et al, 2007; Rottbøll and Friis, 2014; Rottbøll and Friis, 2016; Yang et al, 2017) and rat (Araujo et al, 2008; Bernardi et al, 2017). In the present study, we used microdialysis to determine the pharmacokinetics of cefquinome in the thigh muscle of mice and compared the difference between pharmacokinetics in the plasma and thigh in animal models with different physical statuses.…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacokinetics of antibiotics have been recently studied in some organs such as the lung. One group (Yang et al, 2017) used microdialysis to evaluate the pharmacokinetics of florfenicol in the lung after a single intramuscular administration. Another group (Bernardi et al, 2017) applied microdialysis to evaluate the lung penetration of tobramycin in rats.…”

Section: Introductionmentioning

confidence: 99%

Microdialysis Determination of Cefquinome Pharmacokinetics in Murine Thigh From Healthy, Neutropenic, and Actinobacillus pleuropneumoniae-Infected Mice

et al. 2019

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This study was aimed at applying microdialysis to explore cefquinome pharmacokinetics in thigh and plasma of healthy, neutropenic, and Actinobacillus pleuropneumoniae-infected mice. The relative recoveries (RRs) were tested in vitro by dialysis and retrodialysis and in vivo by retrodialysis. ICR mice were randomly divided into four groups: H-40 (healthy mice receiving cefquinome at 40 mg/kg), H-160, N-40 (neutropenic mice), and I-40 mg/kg (thigh infected-mice with A. pleuropneumoniae). After cefquinome administration, plasma was collected by retro-orbital puncture and thigh dialysate was collected by using a microdialysis probe with Ringer’s solution at a perfusion rate of 1.5 μL/min. Plasma and thigh dialysate samples were assessed by HPLC–MS/MS and analyzed by a non-compartment model. The mean in vivo recoveries in the thigh were 39.35, 38.59, and 37.29% for healthy, neutropenic, and infected mice, respectively. The mean plasma protein-binding level was 16.40% and was independent of drug concentrations. For all groups, the mean values of the free AUCinf in plasma were higher than those in murine thigh, while the elimination T1/2β for plasma were lower than those for murine thigh. Cefquinome penetration (AUCthigh/AUCplasma) from the plasma to thigh was 0.76, 0.88, 0.47, and 0.98 for H-40, N-40, I-40, and H-160 mg/kg, respectively. These results indicated that infection significantly affected cefquinome pharmacokinetics in murine thigh. In conclusion, we successfully applied a microdialysis method to evaluate the pharmacokinetics of cefquinome in murine thigh of healthy, neutropenic, and A. pleuropneumonia-infected mice and the pharmacokinetics of cefquinome was obviously affected by infection in thigh.

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“…Microdialysis is a microsampling technique that can be used to monitor free drug concentrations in the target tissue with minimal invasion (22). Since it was first developed, microdialysis (23) has been used to study the PK characteristics of several antibacterial drugs, such as tobramycin (24), florfenicol (25), levofloxacin (26), and cefpodoxime (27) in the interstitial fluid of organs. Therefore, it is a suitable method to study the relationships between PK/PD indices of free drugs and the antibacterial effect in target tissues.…”

Section: Introductionmentioning

confidence: 99%

Murine Thigh Microdialysis to Evaluate the Pharmacokinetic/Pharmacodynamic Integration of Cefquinome Against Actinobacillus pleuropneumoniae

Zhang

Zhou

et al. 2020

Front. Vet. Sci.

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This study aimed to explore the application of microdialysis in pharmacokinetic (PK)/pharmacodynamic (PD) integration of cefquinome against Actinobacillus pleuropneumoniae. After the A. pleuropneumoniae population reached 10 6 CFU/thigh, the mice received 0.04, 0.16, 0.63, 2.5, and 10 mg/kg cefquinome by subcutaneous injection. Plasma samples were collected by retro-orbital puncture for 4 h, and thigh dialysate was obtained by microdialysis at a flow rate of 1.5 µL/min for 6 h for the PK study. For the PD experiment, the infected mice were treated with a 4-fold-increase in the total cefquinome dose, ranging from 0.01 to 10 mg/kg/24 h, divided into one, two, three, four, and eight doses. The number of bacteria was determined and an inhibitory sigmoid maximum effect (E max) model was used to analyse the relationships between PK/PD parameters and efficacy. The mean penetration of cefquinome from plasma to the thigh was 0.591. The PK data for PK/PD integration were obtained by extrapolation. The fittest PK/PD parameter for efficacy evaluation was %fT>MIC (the percentage of time that free drug concentrations exceed the MIC). The magnitudes of %fT>MIC to achieve net bacterial stasis, 1-log 10 CFU reduction, 2-log 10 CFU reduction, and 3-log 10 CFU reduction were 19.56, 28.65, 41.59, and 67.07 % in plasma and 21.74, 36.11, 52.96, and 82.68% in murine thigh, respectively. Microdialysis was first applied to evaluate the PK/PD integration of cefquinome against A. pleuropneumoniae. These results would provide valuable references when we apply microdialysis to study the PK/PD integration model and use cefquinome to treat animal diseases caused by A. pleuropneumoniae.

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Lung microdialysis study of florfenicol in pigs after single intramuscular administration

Cited by 9 publications

References 28 publications

Diffusion‐limited PBPK model for predicting pulmonary pharmacokinetics of florfenicol in pig

Diffusion‐limited PBPK model for predicting pulmonary pharmacokinetics of florfenicol in pig

Microdialysis Determination of Cefquinome Pharmacokinetics in Murine Thigh From Healthy, Neutropenic, and Actinobacillus pleuropneumoniae-Infected Mice

Murine Thigh Microdialysis to Evaluate the Pharmacokinetic/Pharmacodynamic Integration of Cefquinome Against Actinobacillus pleuropneumoniae

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