The “steric-like” inhibitory effect and mechanism of doxycycline on florfenicol metabolism: Interaction risk.
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2022
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Elsevier
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Xu, X., Liu, Y., Guo, M., Martínez, M. A., Ares, I., Lopez-Torres, B., Martínez-Larrañaga, M. R., Wang, X., Anadón, A., & Martínez, M. (2022). The "steric-like" inhibitory effect and mechanism of doxycycline on florfenicol metabolism: Interaction risk. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 169, 113431. https://doi.org/10.1016/j.fct.2022.113431
Abstract
Most of the studies on doxycycline (DOX) and florfenicol (FF) remain focused on the improvement of antimicrobial activity and antimicrobial spectrum, and there is no relevant report on whether there is interaction between the two drugs after the combination. This research study evaluated the effect of DOX on FF metabolism in vitro and its mechanisms. The findings of this study showed that DOX inhibits FF metabolism in two ways. Firstly, DOX significantly inhibits the expression of CYP3A29, leading to the slower metabolism of FF; secondly, DOX affects the binding of FF to R106 and R372 by competing for the R372 and/or by a "steric-like effect", thus slowing down FF metabolism, which may increase the residual concentration of FF in edible tissues of food producing animals.
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Xiaoqing Xu: Conceptualization, Funding acquisition, Methodology, Validation, Formal analysis, Investigation, Writing – original draft, Writing – review & editing. Yanan Liu: Investigation, Methodology, Formal analysis, Writing original draft, Writing – review & editing. Mingyue Guo: Investigation, Formal analysis, Writing – review & editing. María-Aránzazu Martínez: Investigation, Formal analysis, Writing – review & editing. Irma Ares: Investigation, Formal analysis, Writing – review & editing. Bernardo Lopez-Torres: Investigation, Formal analysis, Writing – review & editing. Xu Wang: Conceptualization, Funding acquisition, Methodology, Validation, Formal analysis, Investigation. Arturo Anadón: Conceptualization, Funding acquisition, Methodology, Valida-tion, Formal analysis, Investigation. Marta Martínez: Conceptualization, Methodology, Investigation, Formal analysis, Writing – review & editing, Conceptualization, Funding acquisition, Methodology, Valida-tion, Formal analysis, Investigation.