PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci

Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk admi...

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Autores principales:	Augusto Matías Lorenzutti, Juan Pablo Vico, Juan Manuel Serrano-Rodríguez, Martín Alejandro Himelfarb, Manuel Ignacio San Andrés-Larrea, José Julio de Lucas-Burneo, Nicolás Javier Litterio
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	marbofloxacin pharmacokinetic pharmacodynamic mastitis goats coagulase negative staphylococci Veterinary medicine SF600-1100 Zoology QL1-991
Acceso en línea:	https://doaj.org/article/f26c691aecde405aa1c022eb05054097
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spelling	oai:doaj.org-article:f26c691aecde405aa1c022eb050540972021-11-25T16:15:15ZPK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci10.3390/ani111130982076-2615https://doaj.org/article/f26c691aecde405aa1c022eb050540972021-10-01T00:00:00Zhttps://www.mdpi.com/2076-2615/11/11/3098https://doaj.org/toc/2076-2615Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci; (ii) to characterize the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk; (iii) to determine AUC/MIC cutoff values of marbofloxacin, and (iv) to perform a PK/PD analysis to evaluate the efficacy of the dose regimen for the treatment of goat mastitis produced by coagulase-negative staphylococci. Marbofloxacin presented context-sensitive pharmacokinetics, influenced by the evolution of the disease, which decreased marbofloxacin disposition in serum and milk. Marbofloxacin showed a median (95% CI) <i>f</i>AUC/MIC values for MIC of 0.4 and 0.8 µg/mL of 26.66 (22.26–36.64) and 32.28 (26.57–48.35) related with −2 log<sub>10</sub>CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log<sub>10</sub>CFU/mL reduction in Mueller Hinton broth. For milk, −2 log<sub>10</sub>CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log<sub>10</sub>CFU/mL reduction with 51.04 (41.6–82.1) and 65.65 (46.68–210.16). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that <i>f</i>AUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.Augusto Matías LorenzuttiJuan Pablo VicoJuan Manuel Serrano-RodríguezMartín Alejandro HimelfarbManuel Ignacio San Andrés-LarreaJosé Julio de Lucas-BurneoNicolás Javier LitterioMDPI AGarticlemarbofloxacinpharmacokineticpharmacodynamicmastitisgoatscoagulase negative staphylococciVeterinary medicineSF600-1100ZoologyQL1-991ENAnimals, Vol 11, Iss 3098, p 3098 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	marbofloxacin pharmacokinetic pharmacodynamic mastitis goats coagulase negative staphylococci Veterinary medicine SF600-1100 Zoology QL1-991
spellingShingle	marbofloxacin pharmacokinetic pharmacodynamic mastitis goats coagulase negative staphylococci Veterinary medicine SF600-1100 Zoology QL1-991 Augusto Matías Lorenzutti Juan Pablo Vico Juan Manuel Serrano-Rodríguez Martín Alejandro Himelfarb Manuel Ignacio San Andrés-Larrea José Julio de Lucas-Burneo Nicolás Javier Litterio PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci
description	Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci; (ii) to characterize the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk; (iii) to determine AUC/MIC cutoff values of marbofloxacin, and (iv) to perform a PK/PD analysis to evaluate the efficacy of the dose regimen for the treatment of goat mastitis produced by coagulase-negative staphylococci. Marbofloxacin presented context-sensitive pharmacokinetics, influenced by the evolution of the disease, which decreased marbofloxacin disposition in serum and milk. Marbofloxacin showed a median (95% CI) <i>f</i>AUC/MIC values for MIC of 0.4 and 0.8 µg/mL of 26.66 (22.26–36.64) and 32.28 (26.57–48.35) related with −2 log<sub>10</sub>CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log<sub>10</sub>CFU/mL reduction in Mueller Hinton broth. For milk, −2 log<sub>10</sub>CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log<sub>10</sub>CFU/mL reduction with 51.04 (41.6–82.1) and 65.65 (46.68–210.16). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that <i>f</i>AUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.
format	article
author	Augusto Matías Lorenzutti Juan Pablo Vico Juan Manuel Serrano-Rodríguez Martín Alejandro Himelfarb Manuel Ignacio San Andrés-Larrea José Julio de Lucas-Burneo Nicolás Javier Litterio
author_facet	Augusto Matías Lorenzutti Juan Pablo Vico Juan Manuel Serrano-Rodríguez Martín Alejandro Himelfarb Manuel Ignacio San Andrés-Larrea José Julio de Lucas-Burneo Nicolás Javier Litterio
author_sort	Augusto Matías Lorenzutti
title	PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci
title_short	PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci
title_full	PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci
title_fullStr	PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci
title_full_unstemmed	PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci
title_sort	pk/pd analysis by nonlinear mixed-effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase-negative staphylococci
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f26c691aecde405aa1c022eb05054097
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PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci

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