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Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model

Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study wer...

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Autores principales: Temmerman, Robin, Pelligand, Ludovic, Schelstraete, Wim, Antonissen, Gunther, Garmyn, An, Devreese, Mathias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161238/
https://www.ncbi.nlm.nih.gov/pubmed/34069540
http://dx.doi.org/10.3390/antibiotics10050604
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author Temmerman, Robin
Pelligand, Ludovic
Schelstraete, Wim
Antonissen, Gunther
Garmyn, An
Devreese, Mathias
author_facet Temmerman, Robin
Pelligand, Ludovic
Schelstraete, Wim
Antonissen, Gunther
Garmyn, An
Devreese, Mathias
author_sort Temmerman, Robin
collection PubMed
description Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to evaluate the pharmacokinetics (PK) of enrofloxacin following IV, PO and drinking water administration. Second, to predict the efficacy of a range of doses in the drinking water for the treatment of APEC infections. For the first objective, PK parameters were estimated by fitting a one-compartmental model with a zero-order IV infusion and an oral absorption lag function to the simultaneously modelled IV and PO data. After fixing these parameter values, a drinking behaviour pharmacokinetic (DBPK) model was developed for the description and prediction of drinking water PK profiles by adding three model improvements (different diurnal and nocturnal drinking rates, inter-animal variability in water consumption and taking account of dose non-proportionality). The subsequent simulations and probability of target attainment (PTA) analysis predicted that a dose of 12.5 mg/kg/24 h is efficacious in treating colibacillosis with an MIC up to 0.125 μg/mL (ECOFF), whereas the currently registered dose (10 mg/kg/24 h) reaches a PTA of 66% at ECOFF.
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spelling pubmed-81612382021-05-29 Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model Temmerman, Robin Pelligand, Ludovic Schelstraete, Wim Antonissen, Gunther Garmyn, An Devreese, Mathias Antibiotics (Basel) Article Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to evaluate the pharmacokinetics (PK) of enrofloxacin following IV, PO and drinking water administration. Second, to predict the efficacy of a range of doses in the drinking water for the treatment of APEC infections. For the first objective, PK parameters were estimated by fitting a one-compartmental model with a zero-order IV infusion and an oral absorption lag function to the simultaneously modelled IV and PO data. After fixing these parameter values, a drinking behaviour pharmacokinetic (DBPK) model was developed for the description and prediction of drinking water PK profiles by adding three model improvements (different diurnal and nocturnal drinking rates, inter-animal variability in water consumption and taking account of dose non-proportionality). The subsequent simulations and probability of target attainment (PTA) analysis predicted that a dose of 12.5 mg/kg/24 h is efficacious in treating colibacillosis with an MIC up to 0.125 μg/mL (ECOFF), whereas the currently registered dose (10 mg/kg/24 h) reaches a PTA of 66% at ECOFF. MDPI 2021-05-19 /pmc/articles/PMC8161238/ /pubmed/34069540 http://dx.doi.org/10.3390/antibiotics10050604 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Temmerman, Robin
Pelligand, Ludovic
Schelstraete, Wim
Antonissen, Gunther
Garmyn, An
Devreese, Mathias
Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model
title Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model
title_full Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model
title_fullStr Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model
title_full_unstemmed Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model
title_short Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model
title_sort enrofloxacin dose optimization for the treatment of colibacillosis in broiler chickens using a drinking behaviour pharmacokinetic model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161238/
https://www.ncbi.nlm.nih.gov/pubmed/34069540
http://dx.doi.org/10.3390/antibiotics10050604
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