Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats

[Background]: Fibromyalgia syndrome (FMS) is a chronic pain condition with widespread pain and multiple comorbidities, for which conventional therapies offer limited benefits. The reserpine-induced myalgia (RIM) model is an efficient animal model of FMS in rodents. This study aimed to develop a phar...

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Autores: Alfosea-Cuadrado, Gloria M., Zarzoso-Foj, Javier, Adell, Albert, Valverde-Navarro, Alfonso A., González-Soler, Eva M., Mangas-Sanjuán, Víctor, Blasco-Serra, Arantxa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/382563
Acceso en línea:http://hdl.handle.net/10261/382563
Access Level:acceso abierto
Palabra clave:Reserpine
Pharmacokinetic
Pharmacodynamic
Fibromyalgia
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spelling Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in RatsAlfosea-Cuadrado, Gloria M.Zarzoso-Foj, JavierAdell, AlbertValverde-Navarro, Alfonso A.González-Soler, Eva M.Mangas-Sanjuán, VíctorBlasco-Serra, ArantxaReserpinePharmacokineticPharmacodynamicFibromyalgia[Background]: Fibromyalgia syndrome (FMS) is a chronic pain condition with widespread pain and multiple comorbidities, for which conventional therapies offer limited benefits. The reserpine-induced myalgia (RIM) model is an efficient animal model of FMS in rodents. This study aimed to develop a pharmacokinetic–pharmacodynamic (PK–PD) model of reserpine in rats, linking to its impact on monoamines (MAs).[Methods]: Reserpine was administered daily for three consecutive days at dose levels of 0.1, 0.5, and 1 mg/kg. A total of 120 rats were included, and 120 PK and 828 PD observations were collected from 48 to 96 h after the first dose of reserpine. Non-linear mixed-effect data analysis was applied for structural PK–PD model definition, variability characterization, and covariate analysis.[Results]: A one-compartment model best described reserpine in rats (V = 1.3 mL/kg and CL = 4.5 × 10−1 mL/h/kg). A precursor-pool PK–PD model (kin = 6.1 × 10−3 mg/h, kp = 8.6 × 10−4 h−1 and kout = 2.7 × 10−2 h−1) with a parallel transit chain (k0 = 1.9 × 10−1 h−1) characterized the longitudinal levels of MA in the prefrontal cortex, spinal cord, and amygdala in rats. Reserpine stimulates the degradation of MA from the pool compartment (Slope1 = 1.1 × 10−1 h) and the elimination of MA (Slope2 = 1.25 h) through the transit chain. Regarding the reference dose (1 mg/kg) of the RIM model, the administration of 4 mg/kg would lead to a mean reduction of 65% (Cmax), 80% (Cmin), and 70% (AUC) of MA across the brain regions tested.[Conclusions]: Regional brain variations in neurotransmitter depletion were identified, particularly in the amygdala, offering insights for therapeutic strategies and biomarker identification in FMS research.This research was funded by Conselleria d’Innovació, Universitats, Ciència i Societat Digital of the Generalitat Valenciana. References GV/2018/049, and CIGE/2022/148.Peer reviewedMultidisciplinary Digital Publishing InstituteGeneralitat ValencianaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/382563reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/pharmaceutics16081101https://doi.org/10.3390/pharmaceutics16081101Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3825632026-05-22T06:33:51Z
dc.title.none.fl_str_mv Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats
title Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats
spellingShingle Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats
Alfosea-Cuadrado, Gloria M.
Reserpine
Pharmacokinetic
Pharmacodynamic
Fibromyalgia
title_short Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats
title_full Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats
title_fullStr Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats
title_full_unstemmed Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats
title_sort Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats
dc.creator.none.fl_str_mv Alfosea-Cuadrado, Gloria M.
Zarzoso-Foj, Javier
Adell, Albert
Valverde-Navarro, Alfonso A.
González-Soler, Eva M.
Mangas-Sanjuán, Víctor
Blasco-Serra, Arantxa
author Alfosea-Cuadrado, Gloria M.
author_facet Alfosea-Cuadrado, Gloria M.
Zarzoso-Foj, Javier
Adell, Albert
Valverde-Navarro, Alfonso A.
González-Soler, Eva M.
Mangas-Sanjuán, Víctor
Blasco-Serra, Arantxa
author_role author
author2 Zarzoso-Foj, Javier
Adell, Albert
Valverde-Navarro, Alfonso A.
González-Soler, Eva M.
Mangas-Sanjuán, Víctor
Blasco-Serra, Arantxa
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Generalitat Valenciana
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Reserpine
Pharmacokinetic
Pharmacodynamic
Fibromyalgia
topic Reserpine
Pharmacokinetic
Pharmacodynamic
Fibromyalgia
description [Background]: Fibromyalgia syndrome (FMS) is a chronic pain condition with widespread pain and multiple comorbidities, for which conventional therapies offer limited benefits. The reserpine-induced myalgia (RIM) model is an efficient animal model of FMS in rodents. This study aimed to develop a pharmacokinetic–pharmacodynamic (PK–PD) model of reserpine in rats, linking to its impact on monoamines (MAs).
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/382563
url http://hdl.handle.net/10261/382563
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/pharmaceutics16081101
https://doi.org/10.3390/pharmaceutics16081101
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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