Pk/pd analysis by nonlinear mixed‐effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase‐negative staphylococci

Autores
Lorenzutti, Augusto Matías; Vico, Juan Pablo; Serrano Rodríguez, Juan Manuel; Himelfarb, Martin Alejandro; San Andrés Larrea, Manuel Ignacio; Lucas Burneo, José Julio de; Litterio, Nicolas Javier
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Coagulase‐negative staphylococci are main pathogens that produce goat mastitis. Mar-bofloxacin is a third‐generation fluoroquinolone approved for treat mastitis in animals. The objec-tives 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 coag-ulase‐negative staphylococci; (ii) to characterize the concentration–effect relationship of marboflox-acin 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) fAUC/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 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/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 marboflox-acin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.
Fil: Lorenzutti, Augusto Matías. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; Argentina. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Fil: Vico, Juan Pablo. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; Argentina
Fil: Serrano Rodríguez, Juan Manuel. Universidad de Córdoba; España
Fil: Himelfarb, Martin Alejandro. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Fil: San Andrés Larrea, Manuel Ignacio. Universidad Complutense de Madrid; España
Fil: Lucas Burneo, José Julio de. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Litterio, Nicolas Javier. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Materia
COAGULASE NEGATIVE STAPHYLOCOCCI
GOATS
MARBOFLOXACIN
MASTITIS
PHARMACODYNAMIC
PHARMACOKINETIC
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182364
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/182364
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pk/pd analysis by nonlinear mixed‐effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase‐negative staphylococciLorenzutti, Augusto MatíasVico, Juan PabloSerrano Rodríguez, Juan ManuelHimelfarb, Martin AlejandroSan Andrés Larrea, Manuel IgnacioLucas Burneo, José Julio deLitterio, Nicolas JavierCOAGULASE NEGATIVE STAPHYLOCOCCIGOATSMARBOFLOXACINMASTITISPHARMACODYNAMICPHARMACOKINETIChttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Coagulase‐negative staphylococci are main pathogens that produce goat mastitis. Mar-bofloxacin is a third‐generation fluoroquinolone approved for treat mastitis in animals. The objec-tives 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 coag-ulase‐negative staphylococci; (ii) to characterize the concentration–effect relationship of marboflox-acin 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) fAUC/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 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/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 marboflox-acin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.Fil: Lorenzutti, Augusto Matías. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; Argentina. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Vico, Juan Pablo. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; ArgentinaFil: Serrano Rodríguez, Juan Manuel. Universidad de Córdoba; EspañaFil: Himelfarb, Martin Alejandro. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: San Andrés Larrea, Manuel Ignacio. Universidad Complutense de Madrid; EspañaFil: Lucas Burneo, José Julio de. Universidad Complutense de Madrid. Facultad de Veterinaria; EspañaFil: Litterio, Nicolas Javier. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaMDPI2021-10-29info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182364Lorenzutti, Augusto Matías; Vico, Juan Pablo; Serrano Rodríguez, Juan Manuel; Himelfarb, Martin Alejandro; San Andrés Larrea, Manuel Ignacio; et al.; Pk/pd analysis by nonlinear mixed‐effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase‐negative staphylococci; MDPI; Animals; 11; 11; 29-10-2021; 1-202076-2615CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-2615/11/11/3098info:eu-repo/semantics/altIdentifier/doi/10.3390/ani11113098info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:29Zoai:ri.conicet.gov.ar:11336/182364instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:51:30.168CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pk/pd analysis by nonlinear mixed‐effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase‐negative staphylococci
title Pk/pd analysis by nonlinear mixed‐effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase‐negative staphylococci
spellingShingle Pk/pd analysis by nonlinear mixed‐effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase‐negative staphylococci
Lorenzutti, Augusto Matías
COAGULASE NEGATIVE STAPHYLOCOCCI
GOATS
MARBOFLOXACIN
MASTITIS
PHARMACODYNAMIC
PHARMACOKINETIC
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
dc.creator.none.fl_str_mv Lorenzutti, Augusto Matías
Vico, Juan Pablo
Serrano Rodríguez, Juan Manuel
Himelfarb, Martin Alejandro
San Andrés Larrea, Manuel Ignacio
Lucas Burneo, José Julio de
Litterio, Nicolas Javier
author Lorenzutti, Augusto Matías
author_facet Lorenzutti, Augusto Matías
Vico, Juan Pablo
Serrano Rodríguez, Juan Manuel
Himelfarb, Martin Alejandro
San Andrés Larrea, Manuel Ignacio
Lucas Burneo, José Julio de
Litterio, Nicolas Javier
author_role author
author2 Vico, Juan Pablo
Serrano Rodríguez, Juan Manuel
Himelfarb, Martin Alejandro
San Andrés Larrea, Manuel Ignacio
Lucas Burneo, José Julio de
Litterio, Nicolas Javier
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv COAGULASE NEGATIVE STAPHYLOCOCCI
GOATS
MARBOFLOXACIN
MASTITIS
PHARMACODYNAMIC
PHARMACOKINETIC
topic COAGULASE NEGATIVE STAPHYLOCOCCI
GOATS
MARBOFLOXACIN
MASTITIS
PHARMACODYNAMIC
PHARMACOKINETIC
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Coagulase‐negative staphylococci are main pathogens that produce goat mastitis. Mar-bofloxacin is a third‐generation fluoroquinolone approved for treat mastitis in animals. The objec-tives 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 coag-ulase‐negative staphylococci; (ii) to characterize the concentration–effect relationship of marboflox-acin 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) fAUC/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 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/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 marboflox-acin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.
Fil: Lorenzutti, Augusto Matías. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; Argentina. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Fil: Vico, Juan Pablo. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; Argentina
Fil: Serrano Rodríguez, Juan Manuel. Universidad de Córdoba; España
Fil: Himelfarb, Martin Alejandro. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Fil: San Andrés Larrea, Manuel Ignacio. Universidad Complutense de Madrid; España
Fil: Lucas Burneo, José Julio de. Universidad Complutense de Madrid. Facultad de Veterinaria; España
Fil: Litterio, Nicolas Javier. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
description Coagulase‐negative staphylococci are main pathogens that produce goat mastitis. Mar-bofloxacin is a third‐generation fluoroquinolone approved for treat mastitis in animals. The objec-tives 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 coag-ulase‐negative staphylococci; (ii) to characterize the concentration–effect relationship of marboflox-acin 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) fAUC/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 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/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 marboflox-acin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.
publishDate 2021
dc.date.none.fl_str_mv 2021-10-29
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/182364
Lorenzutti, Augusto Matías; Vico, Juan Pablo; Serrano Rodríguez, Juan Manuel; Himelfarb, Martin Alejandro; San Andrés Larrea, Manuel Ignacio; et al.; Pk/pd analysis by nonlinear mixed‐effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase‐negative staphylococci; MDPI; Animals; 11; 11; 29-10-2021; 1-20
2076-2615
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182364
identifier_str_mv Lorenzutti, Augusto Matías; Vico, Juan Pablo; Serrano Rodríguez, Juan Manuel; Himelfarb, Martin Alejandro; San Andrés Larrea, Manuel Ignacio; et al.; Pk/pd analysis by nonlinear mixed‐effects modeling of a marbofloxacin dose regimen for treatment of goat mastitis produced by coagulase‐negative staphylococci; MDPI; Animals; 11; 11; 29-10-2021; 1-20
2076-2615
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3390/ani11113098
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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