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J Agric Food Chem. 2017 Jul 19;65(28):5768-5777. doi: 10.1021/acs.jafc.7b01740. Epub 2017 Jul 5.

Pharmacokinetics of Mequindox and Its Marker Residue 1,4-Bisdesoxymequindox in Swine Following Multiple Oral Gavage and Intramuscular Administration: An Experimental Study Coupled with Population Physiologically Based Pharmacokinetic Modeling.

Author information

1
National Reference Laboratory of Veterinary Drug Residues (SCAU), Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510640, China.
2
Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University , Manhattan, Kansas 66506, United States.

Abstract

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.

KEYWORDS:

food safety; mequindox; physiologically based pharmacokinetic (PBPK) modeling; quinoxaline-N,N-dioxide antibiotics; swine

PMID:
28640606
DOI:
10.1021/acs.jafc.7b01740
[Indexed for MEDLINE]

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