Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers

Autores
Höcht, Christian; DiVerniero, Carla; Opezzo, Javier A. W.; Taira, Carlos Alberto
Año de publicación
2005
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction: The aim of the present work was to examine microdialysis as a technique for the study of pharmacokinetic-pharmacodynamic modeling of antihypertensive drugs. For this purpose, we studied the antihypertensive and the chronotropic effect of metoprolol and its plasma concentrations in sham operated (SO) and aortic coarctated (ACo) rats at an early hypertensive stage. Methods: Plasma metoprolol concentrations were obtained by means of a "shunt" vascular microdialysis probe. Changes in mean arterial pressure and heart rate were also measured in the same experiment. Results: A rapid decay of metoprolol levels was observed in both experimental groups. For the chronotropic effect, a good association between plasma levels and the chronotropic effect was observed in SO and ACo rats. ACo rats had a greater sensitivity to the chronotropic effect (Emax:-38±2%, n=5, p<0.05) than SO animals (Emax:-27±1%, n=5). A delay in the blood pressure reduction induced by metoprolol was observed in both experimental groups. A good association was observed between concentrations of metoprolol in the effect compartment and the corresponding hypotensive effect in both experimental groups. The calculated PK-PD parameters were not different between SO and ACo groups. Discussion: A good correlation was found between metoprolol concentration and its chronotropic and antihypertensive effects in normotensive and ACo hypertensive rats, allowing the employment of PK-PD models. The microdialysis technique allows simultaneous determination of plasma levels of antihypertensive drugs and their cardiovascular effects, and is therefore a powerful tool for PK-PD modeling.
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: DiVerniero, Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Opezzo, Javier A. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
"SHUNT" VASCULAR PROBE
AORTIC COARCTATION
CARDIOVASCULAR EFFECTS
METOPROLOL
MICRODIALYSIS
PHARMACOKINETIC-PHARMACODYNAMIC MODELS
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:11336/162289
Acceder
id CONICETDig_e81399c8610649349c3a36b2019e9a44
oai_identifier_str oai:ri.conicet.gov.ar:11336/162289
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockersHöcht, ChristianDiVerniero, CarlaOpezzo, Javier A. W.Taira, Carlos Alberto"SHUNT" VASCULAR PROBEAORTIC COARCTATIONCARDIOVASCULAR EFFECTSMETOPROLOLMICRODIALYSISPHARMACOKINETIC-PHARMACODYNAMIC MODELShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Introduction: The aim of the present work was to examine microdialysis as a technique for the study of pharmacokinetic-pharmacodynamic modeling of antihypertensive drugs. For this purpose, we studied the antihypertensive and the chronotropic effect of metoprolol and its plasma concentrations in sham operated (SO) and aortic coarctated (ACo) rats at an early hypertensive stage. Methods: Plasma metoprolol concentrations were obtained by means of a "shunt" vascular microdialysis probe. Changes in mean arterial pressure and heart rate were also measured in the same experiment. Results: A rapid decay of metoprolol levels was observed in both experimental groups. For the chronotropic effect, a good association between plasma levels and the chronotropic effect was observed in SO and ACo rats. ACo rats had a greater sensitivity to the chronotropic effect (Emax:-38±2%, n=5, p<0.05) than SO animals (Emax:-27±1%, n=5). A delay in the blood pressure reduction induced by metoprolol was observed in both experimental groups. A good association was observed between concentrations of metoprolol in the effect compartment and the corresponding hypotensive effect in both experimental groups. The calculated PK-PD parameters were not different between SO and ACo groups. Discussion: A good correlation was found between metoprolol concentration and its chronotropic and antihypertensive effects in normotensive and ACo hypertensive rats, allowing the employment of PK-PD models. The microdialysis technique allows simultaneous determination of plasma levels of antihypertensive drugs and their cardiovascular effects, and is therefore a powerful tool for PK-PD modeling.Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: DiVerniero, Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Opezzo, Javier A. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaElsevier2005-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162289Höcht, Christian; DiVerniero, Carla; Opezzo, Javier A. W.; Taira, Carlos Alberto; Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers; Elsevier; Journal Of Pharmacological And Toxicological Methods.; 52; 2; 9-2005; 244-2501056-8719CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1056871905000122info:eu-repo/semantics/altIdentifier/doi/10.1016/j.vascn.2005.01.002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:26Zoai:ri.conicet.gov.ar:11336/162289instacron: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 10:11:26.589CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers
title Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers
spellingShingle Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers
Höcht, Christian
"SHUNT" VASCULAR PROBE
AORTIC COARCTATION
CARDIOVASCULAR EFFECTS
METOPROLOL
MICRODIALYSIS
PHARMACOKINETIC-PHARMACODYNAMIC MODELS
title_short Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers
title_full Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers
title_fullStr Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers
title_full_unstemmed Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers
title_sort Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers
dc.creator.none.fl_str_mv Höcht, Christian
DiVerniero, Carla
Opezzo, Javier A. W.
Taira, Carlos Alberto
author Höcht, Christian
author_facet Höcht, Christian
DiVerniero, Carla
Opezzo, Javier A. W.
Taira, Carlos Alberto
author_role author
author2 DiVerniero, Carla
Opezzo, Javier A. W.
Taira, Carlos Alberto
author2_role author
author
author
dc.subject.none.fl_str_mv "SHUNT" VASCULAR PROBE
AORTIC COARCTATION
CARDIOVASCULAR EFFECTS
METOPROLOL
MICRODIALYSIS
PHARMACOKINETIC-PHARMACODYNAMIC MODELS
topic "SHUNT" VASCULAR PROBE
AORTIC COARCTATION
CARDIOVASCULAR EFFECTS
METOPROLOL
MICRODIALYSIS
PHARMACOKINETIC-PHARMACODYNAMIC MODELS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Introduction: The aim of the present work was to examine microdialysis as a technique for the study of pharmacokinetic-pharmacodynamic modeling of antihypertensive drugs. For this purpose, we studied the antihypertensive and the chronotropic effect of metoprolol and its plasma concentrations in sham operated (SO) and aortic coarctated (ACo) rats at an early hypertensive stage. Methods: Plasma metoprolol concentrations were obtained by means of a "shunt" vascular microdialysis probe. Changes in mean arterial pressure and heart rate were also measured in the same experiment. Results: A rapid decay of metoprolol levels was observed in both experimental groups. For the chronotropic effect, a good association between plasma levels and the chronotropic effect was observed in SO and ACo rats. ACo rats had a greater sensitivity to the chronotropic effect (Emax:-38±2%, n=5, p<0.05) than SO animals (Emax:-27±1%, n=5). A delay in the blood pressure reduction induced by metoprolol was observed in both experimental groups. A good association was observed between concentrations of metoprolol in the effect compartment and the corresponding hypotensive effect in both experimental groups. The calculated PK-PD parameters were not different between SO and ACo groups. Discussion: A good correlation was found between metoprolol concentration and its chronotropic and antihypertensive effects in normotensive and ACo hypertensive rats, allowing the employment of PK-PD models. The microdialysis technique allows simultaneous determination of plasma levels of antihypertensive drugs and their cardiovascular effects, and is therefore a powerful tool for PK-PD modeling.
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: DiVerniero, Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Opezzo, Javier A. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Introduction: The aim of the present work was to examine microdialysis as a technique for the study of pharmacokinetic-pharmacodynamic modeling of antihypertensive drugs. For this purpose, we studied the antihypertensive and the chronotropic effect of metoprolol and its plasma concentrations in sham operated (SO) and aortic coarctated (ACo) rats at an early hypertensive stage. Methods: Plasma metoprolol concentrations were obtained by means of a "shunt" vascular microdialysis probe. Changes in mean arterial pressure and heart rate were also measured in the same experiment. Results: A rapid decay of metoprolol levels was observed in both experimental groups. For the chronotropic effect, a good association between plasma levels and the chronotropic effect was observed in SO and ACo rats. ACo rats had a greater sensitivity to the chronotropic effect (Emax:-38±2%, n=5, p<0.05) than SO animals (Emax:-27±1%, n=5). A delay in the blood pressure reduction induced by metoprolol was observed in both experimental groups. A good association was observed between concentrations of metoprolol in the effect compartment and the corresponding hypotensive effect in both experimental groups. The calculated PK-PD parameters were not different between SO and ACo groups. Discussion: A good correlation was found between metoprolol concentration and its chronotropic and antihypertensive effects in normotensive and ACo hypertensive rats, allowing the employment of PK-PD models. The microdialysis technique allows simultaneous determination of plasma levels of antihypertensive drugs and their cardiovascular effects, and is therefore a powerful tool for PK-PD modeling.
publishDate 2005
dc.date.none.fl_str_mv 2005-09
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/11336/162289
Höcht, Christian; DiVerniero, Carla; Opezzo, Javier A. W.; Taira, Carlos Alberto; Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers; Elsevier; Journal Of Pharmacological And Toxicological Methods.; 52; 2; 9-2005; 244-250
1056-8719
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162289
identifier_str_mv Höcht, Christian; DiVerniero, Carla; Opezzo, Javier A. W.; Taira, Carlos Alberto; Applicability of microdialysis as a technique for pharmacokinetic- pharmacodynamic (PK-PD) modeling of antihypertensive beta-blockers; Elsevier; Journal Of Pharmacological And Toxicological Methods.; 52; 2; 9-2005; 244-250
1056-8719
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.sciencedirect.com/science/article/abs/pii/S1056871905000122
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.vascn.2005.01.002
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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score 13.13397

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