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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/182364
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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 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 Técnicas2025-09-03T09:53:00Zoai: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:34982025-09-03 09:53:00.331CONICET 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 |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-2615/11/11/3098 info:eu-repo/semantics/altIdentifier/doi/10.3390/ani11113098 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess 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/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1842269194405543936 |
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13.13397 |