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

文献类型： 外文期刊

作者： Qian, M. R. 1 ; Wang, Q. Y. 3 ; Yang, H. 1 ; Sun, G. Z. 4 ; Ke, X. B. 4 ; Huang, L. L. 5 ; Gao, J. D. 6 ; Yang, J. J. 4 ; Ya 1 ;

作者机构： 1.Zhejiang Acad Agr Sci, State Key Lab Breeding Base Zhejiang Sustainable, Hangzhou, Zhejiang, Peoples R China

2.Zhejiang Acad Agr Sci, Inst Qual & Stand Agroprod, Hangzhou, Zhejiang, Peoples R China

3.Wuhan Agr Sch, Wuhan, Hubei, Peoples R China

4.Wuhan Inst Bioengn, Hubei Engn Res Ctr Viral Vector, Wuhan, Hubei, Peoples R China

5.Huazhong Agr Univ, MOA Key Lab Food Safety Evaluat, Natl Reference Lab Vet Drug Residues, Wuhan, Hubei, Peoples R China

6.Wuhan Royal Vet Hosp, Wuhan, Hubei, Peoples R China

关键词： diffusion-limited distribution;florfenicol;lung interstitial fluid;physiologically based pharmacokinetic model;pig

期刊名称：JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS （ 影响因子：1.786； 五年影响因子：1.7 ）

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收录情况： SCI

摘要： 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 15mg/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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