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In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration
Salmonella typhimurium is a highly transmissible pathogen in rabbits that causes significant losses. Danofloxacin shows excellent efficacy against S. typhimurium infections. However, there are few reports of the pharmacokinetic/pharmacodynamic (PK/PD) modeling of danofloxacin against this pathogen....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913287/ https://www.ncbi.nlm.nih.gov/pubmed/29719510 http://dx.doi.org/10.3389/fphar.2018.00391 |
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author | Xiao, Xia Pei, Lin Jiang, Li-Jie Lan, Wei-Xuan Xiao, Jia-Yu Jiang, Yon-Jia Wang, Zhi-Qiang |
author_facet | Xiao, Xia Pei, Lin Jiang, Li-Jie Lan, Wei-Xuan Xiao, Jia-Yu Jiang, Yon-Jia Wang, Zhi-Qiang |
author_sort | Xiao, Xia |
collection | PubMed |
description | Salmonella typhimurium is a highly transmissible pathogen in rabbits that causes significant losses. Danofloxacin shows excellent efficacy against S. typhimurium infections. However, there are few reports of the pharmacokinetic/pharmacodynamic (PK/PD) modeling of danofloxacin against this pathogen. The aim of this study was to evaluate the in vivo PK/PD relationship of danofloxacin in rabbits infected with S. typhimurium. We used the reduction of bacterial burden in the blood, liver, spleen, and lung as the target PD endpoints, and determined the PK/PD indexes that best correlated with the efficacy and its corresponding magnitude. Danofloxacin was administrated orally to experimentally S. typhimurium-infected rabbits once daily for three successive days. The concentrations of danofloxacin in the serum and the bacterial burden in the blood, liver, spleen, and lung were determined. The PK/PD relationships of danofloxacin against S. typhimurium were evaluated using a Sigmoid E(max) model. The results showed that the area under the concentration-time curve from 0 to 24 h/minimum inhibitory concentration (AUC(24 h)/MIC) ratio correlated well with the in vivo antibacterial effectiveness in different organs, with an r(2) of 0.8971, 0.9186, 0.9581, and 0.8708 in the blood, liver, spleen, and lung, respectively. The AUC(24 h)/MIC ratios for the bactericidal effect (3 × Log(10) colony forming units/mL reductions) were 121.30, 354.28, 216.64, and 228.66 in the blood, liver, spleen, and lung, respectively, indicating that the in vivo effectiveness of danofloxacin against S. typhimurium using bacterial reduction in different organs as PD endpoints was not identical. This study illustrated that the selection of the target organ for bacterial reduction determination had little effect on best PK/PD parameter determination, but is critical for parameter magnitude calculation in antimicrobial PK/PD modeling, and furthermore, has an impact on the rational dosage optimization process. |
format | Online Article Text |
id | pubmed-5913287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59132872018-05-01 In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration Xiao, Xia Pei, Lin Jiang, Li-Jie Lan, Wei-Xuan Xiao, Jia-Yu Jiang, Yon-Jia Wang, Zhi-Qiang Front Pharmacol Pharmacology Salmonella typhimurium is a highly transmissible pathogen in rabbits that causes significant losses. Danofloxacin shows excellent efficacy against S. typhimurium infections. However, there are few reports of the pharmacokinetic/pharmacodynamic (PK/PD) modeling of danofloxacin against this pathogen. The aim of this study was to evaluate the in vivo PK/PD relationship of danofloxacin in rabbits infected with S. typhimurium. We used the reduction of bacterial burden in the blood, liver, spleen, and lung as the target PD endpoints, and determined the PK/PD indexes that best correlated with the efficacy and its corresponding magnitude. Danofloxacin was administrated orally to experimentally S. typhimurium-infected rabbits once daily for three successive days. The concentrations of danofloxacin in the serum and the bacterial burden in the blood, liver, spleen, and lung were determined. The PK/PD relationships of danofloxacin against S. typhimurium were evaluated using a Sigmoid E(max) model. The results showed that the area under the concentration-time curve from 0 to 24 h/minimum inhibitory concentration (AUC(24 h)/MIC) ratio correlated well with the in vivo antibacterial effectiveness in different organs, with an r(2) of 0.8971, 0.9186, 0.9581, and 0.8708 in the blood, liver, spleen, and lung, respectively. The AUC(24 h)/MIC ratios for the bactericidal effect (3 × Log(10) colony forming units/mL reductions) were 121.30, 354.28, 216.64, and 228.66 in the blood, liver, spleen, and lung, respectively, indicating that the in vivo effectiveness of danofloxacin against S. typhimurium using bacterial reduction in different organs as PD endpoints was not identical. This study illustrated that the selection of the target organ for bacterial reduction determination had little effect on best PK/PD parameter determination, but is critical for parameter magnitude calculation in antimicrobial PK/PD modeling, and furthermore, has an impact on the rational dosage optimization process. Frontiers Media S.A. 2018-04-17 /pmc/articles/PMC5913287/ /pubmed/29719510 http://dx.doi.org/10.3389/fphar.2018.00391 Text en Copyright © 2018 Xiao, Pei, Jiang, Lan, Xiao, Jiang and Wang. http://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 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 | Pharmacology Xiao, Xia Pei, Lin Jiang, Li-Jie Lan, Wei-Xuan Xiao, Jia-Yu Jiang, Yon-Jia Wang, Zhi-Qiang In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration |
title | In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration |
title_full | In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration |
title_fullStr | In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration |
title_full_unstemmed | In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration |
title_short | In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Danofloxacin in Rabbits Infected With Salmonella typhimurium After Oral Administration |
title_sort | in vivo pharmacokinetic/pharmacodynamic profiles of danofloxacin in rabbits infected with salmonella typhimurium after oral administration |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913287/ https://www.ncbi.nlm.nih.gov/pubmed/29719510 http://dx.doi.org/10.3389/fphar.2018.00391 |
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