Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers

Olanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions. Currently, there are no clinical guidelines implementing pharmacogenetic information on olanzapine. Moreover, the Dutch Pharmacogenomics Working Group (DPWG) sta...

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Autores: Zubiaur, Pablo, Soria Chacartegui, Paula, Koller, Dora, Navares-Gómez, Marcos, Ochoa Mazarro, María Dolores, Almenara, Susana, Saiz-Rodríguez, Miriam, Mejía Abril, Gina, Villapalos-García, Gonzalo, Román, Manuel, Martín-Vílchez, Samuel, Abad Santos, Francisco
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/704967
Acesso em linha:http://hdl.handle.net/10486/704967
https://dx.doi.org/10.1016/j.biopha.2020.111087
Access Level:acceso abierto
Palavra-chave:Cytochrome P450
Olanzapine
Pharmacogenetics
Precision medicine
Medicina
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spelling Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteersZubiaur, PabloSoria Chacartegui, PaulaKoller, DoraNavares-Gómez, MarcosOchoa Mazarro, María DoloresAlmenara, SusanaSaiz-Rodríguez, MiriamMejía Abril, GinaVillapalos-García, GonzaloRomán, ManuelMartín-Vílchez, SamuelAbad Santos, FranciscoCytochrome P450OlanzapinePharmacogeneticsPrecision medicineMedicinaOlanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions. Currently, there are no clinical guidelines implementing pharmacogenetic information on olanzapine. Moreover, the Dutch Pharmacogenomics Working Group (DPWG) states that CYP2D6 phenotype is not related to olanzapine response or side effects. Thus, the objective of this candidate-gene study was to investigate the effect of 72 polymorphisms in 21 genes on olanzapine pharmacokinetics and safety, including transporters (e.g. ABCB1, ABCC2, SLC22A1), receptors (e.g. DRD2, HTR2C), and enzymes (e.g. UGT, CYP and COMT), in a cohort of healthy volunteers. Polymorphisms in CYP2C9, SLC22A1, ABCB1, ABCC2, and APOC3 were related to olanzapine pharmacokinetic variability. The incidence of adverse reactions was related to several genes: palpitations to ABCB1 and SLC22A1, asthenia to ABCB1, somnolence to DRD2 and ABCB1, and dizziness to CYP2C9. However, further studies in patients are warranted to confirm the influence of these genetic polymorphisms on olanzapine pharmacokinetics and tolerability.D. Koller is financed by the H2020 Marie Sklodowska-Curie Innovative Training Network721236 grant. Marcos Navares-G´omez is cofinaneced by the European Social Fund and the Youth European Initiative, grant number PEJ-2018-TL/MD-11080Elsevier Masson s.r.l.Departamento de FarmacologíaFacultad de Medicina20202020-12-08research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/704967https://dx.doi.org/10.1016/j.biopha.2020.111087reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7049672026-06-23T12:46:27Z
dc.title.none.fl_str_mv Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
title Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
spellingShingle Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
Zubiaur, Pablo
Cytochrome P450
Olanzapine
Pharmacogenetics
Precision medicine
Medicina
title_short Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
title_full Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
title_fullStr Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
title_full_unstemmed Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
title_sort Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
dc.creator.none.fl_str_mv Zubiaur, Pablo
Soria Chacartegui, Paula
Koller, Dora
Navares-Gómez, Marcos
Ochoa Mazarro, María Dolores
Almenara, Susana
Saiz-Rodríguez, Miriam
Mejía Abril, Gina
Villapalos-García, Gonzalo
Román, Manuel
Martín-Vílchez, Samuel
Abad Santos, Francisco
author Zubiaur, Pablo
author_facet Zubiaur, Pablo
Soria Chacartegui, Paula
Koller, Dora
Navares-Gómez, Marcos
Ochoa Mazarro, María Dolores
Almenara, Susana
Saiz-Rodríguez, Miriam
Mejía Abril, Gina
Villapalos-García, Gonzalo
Román, Manuel
Martín-Vílchez, Samuel
Abad Santos, Francisco
author_role author
author2 Soria Chacartegui, Paula
Koller, Dora
Navares-Gómez, Marcos
Ochoa Mazarro, María Dolores
Almenara, Susana
Saiz-Rodríguez, Miriam
Mejía Abril, Gina
Villapalos-García, Gonzalo
Román, Manuel
Martín-Vílchez, Samuel
Abad Santos, Francisco
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Farmacología
Facultad de Medicina
dc.subject.none.fl_str_mv Cytochrome P450
Olanzapine
Pharmacogenetics
Precision medicine
Medicina
topic Cytochrome P450
Olanzapine
Pharmacogenetics
Precision medicine
Medicina
description Olanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions. Currently, there are no clinical guidelines implementing pharmacogenetic information on olanzapine. Moreover, the Dutch Pharmacogenomics Working Group (DPWG) states that CYP2D6 phenotype is not related to olanzapine response or side effects. Thus, the objective of this candidate-gene study was to investigate the effect of 72 polymorphisms in 21 genes on olanzapine pharmacokinetics and safety, including transporters (e.g. ABCB1, ABCC2, SLC22A1), receptors (e.g. DRD2, HTR2C), and enzymes (e.g. UGT, CYP and COMT), in a cohort of healthy volunteers. Polymorphisms in CYP2C9, SLC22A1, ABCB1, ABCC2, and APOC3 were related to olanzapine pharmacokinetic variability. The incidence of adverse reactions was related to several genes: palpitations to ABCB1 and SLC22A1, asthenia to ABCB1, somnolence to DRD2 and ABCB1, and dizziness to CYP2C9. However, further studies in patients are warranted to confirm the influence of these genetic polymorphisms on olanzapine pharmacokinetics and tolerability.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-12-08
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/704967
https://dx.doi.org/10.1016/j.biopha.2020.111087
url http://hdl.handle.net/10486/704967
https://dx.doi.org/10.1016/j.biopha.2020.111087
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier Masson s.r.l.
publisher.none.fl_str_mv Elsevier Masson s.r.l.
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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