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Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus)

When two drugs are combined, drug-drug interactions (DDI) often occur. Metabolic DDI usually occur due to inhibition of the metabolism of one drug by the other. This leads to an increase in the plasma concentration of the drug whose metabolism is inhibited. The objective of this research study was t...

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Autores principales: Wang, Xiaojing, Yang, Yaqin, Martínez, María-Aránzazu, Martínez, Marta, Lopez-Torres, Bernardo, Martínez-Larrañaga, María-Rosa, Wang, Xu, Anadón, Arturo, Ares, Irma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558239/
https://www.ncbi.nlm.nih.gov/pubmed/34733909
http://dx.doi.org/10.3389/fvets.2021.759716
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author Wang, Xiaojing
Yang, Yaqin
Martínez, María-Aránzazu
Martínez, Marta
Lopez-Torres, Bernardo
Martínez-Larrañaga, María-Rosa
Wang, Xu
Anadón, Arturo
Ares, Irma
author_facet Wang, Xiaojing
Yang, Yaqin
Martínez, María-Aránzazu
Martínez, Marta
Lopez-Torres, Bernardo
Martínez-Larrañaga, María-Rosa
Wang, Xu
Anadón, Arturo
Ares, Irma
author_sort Wang, Xiaojing
collection PubMed
description When two drugs are combined, drug-drug interactions (DDI) often occur. Metabolic DDI usually occur due to inhibition of the metabolism of one drug by the other. This leads to an increase in the plasma concentration of the drug whose metabolism is inhibited. The objective of this research study was to verify the DDI risk of two antibacterial, florfenicol (FF) and doxycycline (DOX) due to metabolism. Because food containing residues of any pharmacologically active substance could potentially constitute a public health hazard, we selected a food producing animal, goat, goat liver microsomes and recombinant metabolic enzymes, for in vivo and in vitro metabolism studies. In vitro experiments showed that CYP3A was the key enzyme subfamily in FF metabolism, DOX slowed down FF metabolism and R440 was possibly the key amino acid in the metabolic interaction between FF and DOX. In vivo studies in the goats showed that DOX inhibited up-regulation of CYP3A24 gene expression produced by FF; in liver and kidney, DOX slightly slowed down FF metabolism. Quantitative prediction of DDI risk suggest that when DOX is used in combination with FF in veterinary medicine, may result in a clinical significant increase of FF plasma and tissue concentrations, resulting a prevalence of harmful tissue residues of medicinal products in the food chain. Through our experimentation, when DOX is used in combination with FF, the withdrawal period of FF in the kidney was extended by 1 day. Otherwise, an appropriate withdrawal period (20 days) of FF was established for FF and DOX combined use to ensure that the animal can be safely slaughtered for food.
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spelling pubmed-85582392021-11-02 Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus) Wang, Xiaojing Yang, Yaqin Martínez, María-Aránzazu Martínez, Marta Lopez-Torres, Bernardo Martínez-Larrañaga, María-Rosa Wang, Xu Anadón, Arturo Ares, Irma Front Vet Sci Veterinary Science When two drugs are combined, drug-drug interactions (DDI) often occur. Metabolic DDI usually occur due to inhibition of the metabolism of one drug by the other. This leads to an increase in the plasma concentration of the drug whose metabolism is inhibited. The objective of this research study was to verify the DDI risk of two antibacterial, florfenicol (FF) and doxycycline (DOX) due to metabolism. Because food containing residues of any pharmacologically active substance could potentially constitute a public health hazard, we selected a food producing animal, goat, goat liver microsomes and recombinant metabolic enzymes, for in vivo and in vitro metabolism studies. In vitro experiments showed that CYP3A was the key enzyme subfamily in FF metabolism, DOX slowed down FF metabolism and R440 was possibly the key amino acid in the metabolic interaction between FF and DOX. In vivo studies in the goats showed that DOX inhibited up-regulation of CYP3A24 gene expression produced by FF; in liver and kidney, DOX slightly slowed down FF metabolism. Quantitative prediction of DDI risk suggest that when DOX is used in combination with FF in veterinary medicine, may result in a clinical significant increase of FF plasma and tissue concentrations, resulting a prevalence of harmful tissue residues of medicinal products in the food chain. Through our experimentation, when DOX is used in combination with FF, the withdrawal period of FF in the kidney was extended by 1 day. Otherwise, an appropriate withdrawal period (20 days) of FF was established for FF and DOX combined use to ensure that the animal can be safely slaughtered for food. Frontiers Media S.A. 2021-10-18 /pmc/articles/PMC8558239/ /pubmed/34733909 http://dx.doi.org/10.3389/fvets.2021.759716 Text en Copyright © 2021 Wang, Yang, Martínez, Martínez, Lopez-Torres, Martínez-Larrañaga, Wang, Anadón and Ares. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Wang, Xiaojing
Yang, Yaqin
Martínez, María-Aránzazu
Martínez, Marta
Lopez-Torres, Bernardo
Martínez-Larrañaga, María-Rosa
Wang, Xu
Anadón, Arturo
Ares, Irma
Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus)
title Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus)
title_full Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus)
title_fullStr Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus)
title_full_unstemmed Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus)
title_short Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus)
title_sort interaction between florfenicol and doxycycline involving cytochrome p450 3a in goats (capra hricus)
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558239/
https://www.ncbi.nlm.nih.gov/pubmed/34733909
http://dx.doi.org/10.3389/fvets.2021.759716
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