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dc.contributor.author
Höcht, Christian
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dc.contributor.author
Di Verniero, Carla
dc.contributor.author
Opezzo, Javier A.
dc.contributor.author
Bramuglia, Guillermo Federico
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dc.contributor.author
Taira, Carlos Alberto
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dc.date.available
2020-08-05T17:08:23Z
dc.date.issued
2006-05
dc.identifier.citation
Höcht, Christian; Di Verniero, Carla; Opezzo, Javier A.; Bramuglia, Guillermo Federico; Taira, Carlos Alberto; Pharmacokinetic-pharmacodynamic (PK-PD) modeling of cardiovascular effects of metoprolol in spontaneously hypertensive rats: a microdialysis study; Springer; Naunyn-schmiedebergs Archives Of Pharmacology; 373; 4; 5-2006; 310-318
dc.identifier.issn
0028-1298
dc.identifier.uri
http://hdl.handle.net/11336/110932
dc.description.abstract
The present work addressed possible alterations inthe pharmacokinetics and the in vivo pharmacodynamic ofmetoprolol (MET) in spontaneously hypertensive (SH) ratsand Wistar Kyoto (WKY) animals by means of the microdialysistechnique. The correlation between MET unboundplasma concentrations and its pharmacological effects, such asheart rate and blood pressure change,was also examined in SHand WKY rats by the application of a PK-PD model. METdialysate concentrations and its chronotropic and bloodpressure effect were determined during 3 h after theadministration of 3 and 10 mg.kg−1 of the drug. A PK-PDmodel with a separate effect compartment was used toanalyse the data. A good correlation between plasma METconcentrations and its hypotensive and chronotropic effectwas found in all experimental groups. Although a greatermaximal effect (Emax) for the antihypertensive effect of METwas observed in SH rats (WKY: Emax: −17±1 mmHg; SH:Emax: −28±4 mmHg; P<0.05 versus WKY rats), no differenceswere found in the concentration yielding half-maximalresponse (IC50) comparing SH (IC50: 583±146 ng.ml−1) andWKY animals (IC50: 639±187 ng.ml−1). The bradycardiceffect of MET was greater in SH rats (Emax: −29±1%, P<0.05versus WKY rats) than in WK animals (Emax: −22±2%), butno differences were observed in the IC50 comparing bothexperimental groups (WKY: IC50: 187±53 ng.ml−1; SH: IC50:216±62 ng.ml−1). Pharmacokinetic analysis shows that thevolume of distribution of MET was greater in SH rats (Vd:3.4±0.5 l, P<0.05 versus WKY rats) with regard to WistarKyoto (WKY) animals (Vd: 1.9±0.2 l). The results suggestthat the pharmacokinetic behaviour of metoprolol aremodified in SH rats, resulting in an increased volume ofdistribution. A greater maximal efficacy to the hypotensiveeffect of metoprolol was observed in SH rats, suggestingparticipation of â-adrenoceptors in the maintenance of thehypertension. Also, a greater chronotropic response tometoprolol was found in the hypertensive group comparedwith WKY animals, suggesting that, at least in part, thegreater cardiac effect of metoprolol explained the enhancedhypotensive response of the beta blocker in the SH animals.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
PK/PD modelling/PD modelling
dc.subject
metoprolol
dc.subject
hypertension model
dc.subject.classification
Farmacología y Farmacia
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Pharmacokinetic-pharmacodynamic (PK-PD) modeling of cardiovascular effects of metoprolol in spontaneously hypertensive rats: a microdialysis study
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-07-21T20:20:55Z
dc.journal.volume
373
dc.journal.number
4
dc.journal.pagination
310-318
dc.journal.pais
Alemania
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dc.description.fil
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
dc.description.fil
Fil: Di Verniero, Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
dc.description.fil
Fil: Opezzo, Javier A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
dc.description.fil
Fil: Bramuglia, Guillermo Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
dc.description.fil
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
dc.journal.title
Naunyn-schmiedebergs Archives Of Pharmacology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00210-006-0078-x
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00210-006-0078-x
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