Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats

Autores
Bertera, Facundo; Di Verniero, Carla Andrea; Mayer, Marcos Alejandro; Chiappetta, Diego Andrés; Buontempo, Fabián; Polizio, Ariel Héctor; Taira, Carlos Alberto; Höcht, Christian
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The cardiovascular effects and mechanism of antihypertensive response of carvedilol were assessed in fructose fed rats using pharmacokinetic–pharmacodynamic (PK-PD) modelling. Male Sprague Dowley rats were randomly divided into two groups: control rats received water for 6 weeks while fructose rats received fructose solution (10 %w/v) during 6 weeks. Effects of carvedilol (1-3 mg/kg i.v.) on blood pressure, heart rate and blood pressure variability were recorded. Enantioselective carvedilol plasma pharmacokinetics was studied by traditional blood sampling. Relationship between carvedilol concentrations and their hypotensive and bradycardic effects was established by PK-PD modelling. Vascular sympatholytic activity of carvedilol was assessed by estimation of drug effects on low frequency blood pressure variability using spectral analysis. A greater volume of distribution and clearance of S-carvedilol compared to R-enantiomer was found in both experimental groups. Fructose feeding increased volume of distribution of both enantiomers. Although PK-PD properties of S-carvedilol chronotropic effect were not altered in fructose rats, hypertensive rats showed greater efficacy to the carvedilol hypotensive response after administration of the higher dose. A similar potency of carvedilol to inhibit sympathetic vascular activity was found in fructose rats. Carvedilol showed enantioselective non-linear pharmacokinetic properties in both groups with increased distribution in fructose fed rats compared with normotensive animals. An enhanced hypotensive activity of carvedilol was found in fructose rats compared with control rats, which is not related to enhanced sympatholytic activity. Therefore, pleiotropic effects of carvedilol, such as antioxidant activity, seem to contribute to its enhanced antihypertensive activity in this experimental model of metabolic syndrome.
Fil: Bertera, Facundo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Di Verniero, Carla Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Mayer, Marcos Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Buontempo, Fabián. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Polizio, Ariel Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Taira, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Materia
Carvedilol
Enantioselective Pharmacokinetics
Hypertension
Pk-Pd Modelling
Sympathetic Vascular Activity
Metabolic Syndrome
Fructose
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:11336/14140
Acceder
id CONICETDig_771e5389a6ef6136b6f66947228cf3be
oai_identifier_str oai:ri.conicet.gov.ar:11336/14140
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive ratsBertera, FacundoDi Verniero, Carla AndreaMayer, Marcos AlejandroChiappetta, Diego AndrésBuontempo, FabiánPolizio, Ariel HéctorTaira, Carlos AlbertoHöcht, ChristianCarvedilolEnantioselective PharmacokineticsHypertensionPk-Pd ModellingSympathetic Vascular ActivityMetabolic SyndromeFructosehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The cardiovascular effects and mechanism of antihypertensive response of carvedilol were assessed in fructose fed rats using pharmacokinetic–pharmacodynamic (PK-PD) modelling. Male Sprague Dowley rats were randomly divided into two groups: control rats received water for 6 weeks while fructose rats received fructose solution (10 %w/v) during 6 weeks. Effects of carvedilol (1-3 mg/kg i.v.) on blood pressure, heart rate and blood pressure variability were recorded. Enantioselective carvedilol plasma pharmacokinetics was studied by traditional blood sampling. Relationship between carvedilol concentrations and their hypotensive and bradycardic effects was established by PK-PD modelling. Vascular sympatholytic activity of carvedilol was assessed by estimation of drug effects on low frequency blood pressure variability using spectral analysis. A greater volume of distribution and clearance of S-carvedilol compared to R-enantiomer was found in both experimental groups. Fructose feeding increased volume of distribution of both enantiomers. Although PK-PD properties of S-carvedilol chronotropic effect were not altered in fructose rats, hypertensive rats showed greater efficacy to the carvedilol hypotensive response after administration of the higher dose. A similar potency of carvedilol to inhibit sympathetic vascular activity was found in fructose rats. Carvedilol showed enantioselective non-linear pharmacokinetic properties in both groups with increased distribution in fructose fed rats compared with normotensive animals. An enhanced hypotensive activity of carvedilol was found in fructose rats compared with control rats, which is not related to enhanced sympatholytic activity. Therefore, pleiotropic effects of carvedilol, such as antioxidant activity, seem to contribute to its enhanced antihypertensive activity in this experimental model of metabolic syndrome.Fil: Bertera, Facundo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Di Verniero, Carla Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Mayer, Marcos Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Buontempo, Fabián. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Polizio, Ariel Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Taira, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaTaylor & Francis2011-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14140Bertera, Facundo; Di Verniero, Carla Andrea; Mayer, Marcos Alejandro; Chiappetta, Diego Andrés; Buontempo, Fabián; et al.; Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats; Taylor & Francis; Xenobiotica; 42; 2; 9-2011; 206-2190049-82541366-5928enginfo:eu-repo/semantics/altIdentifier/doi/10.3109/00498254.2011.604746info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/00498254.2011.604746info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:35:20Zoai:ri.conicet.gov.ar:11336/14140instacron: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 09:35:20.91CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats
title Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats
spellingShingle Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats
Bertera, Facundo
Carvedilol
Enantioselective Pharmacokinetics
Hypertension
Pk-Pd Modelling
Sympathetic Vascular Activity
Metabolic Syndrome
Fructose
title_short Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats
title_full Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats
title_fullStr Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats
title_full_unstemmed Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats
title_sort Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats
dc.creator.none.fl_str_mv Bertera, Facundo
Di Verniero, Carla Andrea
Mayer, Marcos Alejandro
Chiappetta, Diego Andrés
Buontempo, Fabián
Polizio, Ariel Héctor
Taira, Carlos Alberto
Höcht, Christian
author Bertera, Facundo
author_facet Bertera, Facundo
Di Verniero, Carla Andrea
Mayer, Marcos Alejandro
Chiappetta, Diego Andrés
Buontempo, Fabián
Polizio, Ariel Héctor
Taira, Carlos Alberto
Höcht, Christian
author_role author
author2 Di Verniero, Carla Andrea
Mayer, Marcos Alejandro
Chiappetta, Diego Andrés
Buontempo, Fabián
Polizio, Ariel Héctor
Taira, Carlos Alberto
Höcht, Christian
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Carvedilol
Enantioselective Pharmacokinetics
Hypertension
Pk-Pd Modelling
Sympathetic Vascular Activity
Metabolic Syndrome
Fructose
topic Carvedilol
Enantioselective Pharmacokinetics
Hypertension
Pk-Pd Modelling
Sympathetic Vascular Activity
Metabolic Syndrome
Fructose
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The cardiovascular effects and mechanism of antihypertensive response of carvedilol were assessed in fructose fed rats using pharmacokinetic–pharmacodynamic (PK-PD) modelling. Male Sprague Dowley rats were randomly divided into two groups: control rats received water for 6 weeks while fructose rats received fructose solution (10 %w/v) during 6 weeks. Effects of carvedilol (1-3 mg/kg i.v.) on blood pressure, heart rate and blood pressure variability were recorded. Enantioselective carvedilol plasma pharmacokinetics was studied by traditional blood sampling. Relationship between carvedilol concentrations and their hypotensive and bradycardic effects was established by PK-PD modelling. Vascular sympatholytic activity of carvedilol was assessed by estimation of drug effects on low frequency blood pressure variability using spectral analysis. A greater volume of distribution and clearance of S-carvedilol compared to R-enantiomer was found in both experimental groups. Fructose feeding increased volume of distribution of both enantiomers. Although PK-PD properties of S-carvedilol chronotropic effect were not altered in fructose rats, hypertensive rats showed greater efficacy to the carvedilol hypotensive response after administration of the higher dose. A similar potency of carvedilol to inhibit sympathetic vascular activity was found in fructose rats. Carvedilol showed enantioselective non-linear pharmacokinetic properties in both groups with increased distribution in fructose fed rats compared with normotensive animals. An enhanced hypotensive activity of carvedilol was found in fructose rats compared with control rats, which is not related to enhanced sympatholytic activity. Therefore, pleiotropic effects of carvedilol, such as antioxidant activity, seem to contribute to its enhanced antihypertensive activity in this experimental model of metabolic syndrome.
Fil: Bertera, Facundo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Di Verniero, Carla Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Mayer, Marcos Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Buontempo, Fabián. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Polizio, Ariel Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Taira, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
description The cardiovascular effects and mechanism of antihypertensive response of carvedilol were assessed in fructose fed rats using pharmacokinetic–pharmacodynamic (PK-PD) modelling. Male Sprague Dowley rats were randomly divided into two groups: control rats received water for 6 weeks while fructose rats received fructose solution (10 %w/v) during 6 weeks. Effects of carvedilol (1-3 mg/kg i.v.) on blood pressure, heart rate and blood pressure variability were recorded. Enantioselective carvedilol plasma pharmacokinetics was studied by traditional blood sampling. Relationship between carvedilol concentrations and their hypotensive and bradycardic effects was established by PK-PD modelling. Vascular sympatholytic activity of carvedilol was assessed by estimation of drug effects on low frequency blood pressure variability using spectral analysis. A greater volume of distribution and clearance of S-carvedilol compared to R-enantiomer was found in both experimental groups. Fructose feeding increased volume of distribution of both enantiomers. Although PK-PD properties of S-carvedilol chronotropic effect were not altered in fructose rats, hypertensive rats showed greater efficacy to the carvedilol hypotensive response after administration of the higher dose. A similar potency of carvedilol to inhibit sympathetic vascular activity was found in fructose rats. Carvedilol showed enantioselective non-linear pharmacokinetic properties in both groups with increased distribution in fructose fed rats compared with normotensive animals. An enhanced hypotensive activity of carvedilol was found in fructose rats compared with control rats, which is not related to enhanced sympatholytic activity. Therefore, pleiotropic effects of carvedilol, such as antioxidant activity, seem to contribute to its enhanced antihypertensive activity in this experimental model of metabolic syndrome.
publishDate 2011
dc.date.none.fl_str_mv 2011-09
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/11336/14140
Bertera, Facundo; Di Verniero, Carla Andrea; Mayer, Marcos Alejandro; Chiappetta, Diego Andrés; Buontempo, Fabián; et al.; Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats; Taylor & Francis; Xenobiotica; 42; 2; 9-2011; 206-219
0049-8254
1366-5928
url http://hdl.handle.net/11336/14140
identifier_str_mv Bertera, Facundo; Di Verniero, Carla Andrea; Mayer, Marcos Alejandro; Chiappetta, Diego Andrés; Buontempo, Fabián; et al.; Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose hypertensive rats; Taylor & Francis; Xenobiotica; 42; 2; 9-2011; 206-219
0049-8254
1366-5928
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3109/00498254.2011.604746
info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/00498254.2011.604746
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 Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
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 13.070432

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