National Reference Laboratory of Veterinary Drug Residues (SCAU), Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510640, China.
Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University , Manhattan, Kansas 66506, United States.
J Agric Food Chem. 2017 Jul 19;65(28):5768-5777. doi: 10.1021/acs.jafc.7b01740. Epub 2017 Jul 5.
Mequindox (MEQ) is a quinoxaline-N,N-dioxide antibiotic used in food-producing animals. MEQ residue in animal-derived foods is a food safety concern. The tissue distribution of MEQ and its marker residue 1,4-bisdesoxymequindox (M1) were determined in swine following oral gavage or intramuscular injection twice daily for 3 days. The experimental data were used to construct a flow-limited physiologically based pharmacokinetic (PBPK) model. The model predictions correlated with available data well. Monte Carlo analysis showed that the times needed for M1 concentrations to fall below limit of detection (5 μg/kg) in liver for the 99th percentile of the population were 27 and 34 days after oral gavage and intramuscular administration twice daily for 3 days, respectively. This population PBPK model can be used to predict depletion kinetic profiles and tissue residues of MEQ's marker residue M1 in swine and as a foundation for scaling to other quinoxaline-N,N-dioxide antibiotics and to other animal species.
美喹多司（MEQ）是一种用于食用动物的喹喔啉-N,N-二氧化物抗生素。动物源性食品中的 MEQ 残留是食品安全关注的问题。本研究通过每日两次经口灌胃或肌肉注射 MEQ 连续 3 天，在猪体内研究 MEQ 及其标记物 1,4-双去甲氧美喹多司（M1）的组织分布。实验数据用于构建一个血流限制型基于生理学的药代动力学（PBPK）模型。模型预测与可用数据吻合良好。蒙特卡罗分析表明，经口灌胃和肌肉注射每日两次连续 3 天后，人群第 99 百分位个体的肝脏中 M1 浓度降至检测限（5μg/kg）以下所需的时间分别为 27 天和 34 天。该群体 PBPK 模型可用于预测 MEQ 标记物 M1 在猪体内的消除动力学曲线和组织残留，并为其他喹喔啉-N,N-二氧化物抗生素和其他动物物种的缩放提供基础。
