A physiologically based pharmacokinetic model of doxycycline for predicting tissue residues and withdrawal intervals in grass carp (Ctenopharyngodon idella)
文献类型： 外文期刊
作者： Xu, Ning 1 ; Li, Miao 1 ; Chou, Wei-Chun 1 ; Lin, Zhoumeng 1 ;
作者机构： 1.Kansas State Univ, Coll Vet Med, Inst Computat Comparat Med, Dept Anat & Physiol, 1800 Denison Ave,P200 Mosier Hall, Manhattan, KS 66506 USA
2.Chinese Acad Fishery Sci, Yangtze River Fisheries Res Inst, Wuhan 430223, Peoples R China
关键词： Doxycycline; Physiologically based pharmacokinetic (PBPK) model; Grass carp; Drug residue; Withdrawal time; Food safety
期刊名称：FOOD AND CHEMICAL TOXICOLOGY （ 影响因子：6.023； 五年影响因子：5.844 ）
ISSN： 0278-6915
年卷期： 2020 年 137 卷
页码：
收录情况： SCI
摘要： The extensive use of doxycycline in aquaculture results in drug residue violations that negatively impact human food safety. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for doxycycline to predict drug residues and withdrawal times (WTs) in grass carp (Ctenopharyngodon idella) after daily oral administration for 3 days. Physiological parameters including cardiac output and organ weights were measured experimentally. Chemical-specific parameters were obtained from the literature or estimated by fitting to the observed data. The model properly captured the observed kinetic profiles of doxycycline in tissues (i.e., liver, kidney, muscle + skin and gill). The predicted WT in muscle + skin by Monte Carlo analysis based on sensitive parameters identified at 24 h after drug administration was 41 d, which was similar to 43 d calculated using the tolerance limit method. Sensitivity analysis identified two additional sensitive parameters at 6 weeks: intestinal transit rate constant and urinary elimination rate constant. The predicted WT in muscle + skin based on sensitive parameters identified at 6 weeks was 54 d. This model provides a useful tool to estimate tissue residues and withdrawal times for doxycycline in grass carp and also serves a foundation for extrapolation to other fish species and other tetracyclines.
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