Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics

[Introduction] Aripiprazole and olanzapine are atypical antipsychotics. Both drugs can induce metabolic changes; however, the metabolic side effects produced by aripiprazole are more benign. The aim of the study was to evaluate if aripiprazole and olanzapine alter prolactin levels, lipid and glucose...

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Autores: Koller, Dora, Almenara, Susana, Mejía, Gina, Saiz-Rodríguez, Miriam, Zubiaur, Pablo, Román, Manuel, Ochoa, Dolores, Navares-Gómez, Marcos, Santos-Molina, Elena, Pintos-Sánchez, Elena, Abad-Santos, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/245492
Acceso en línea:http://hdl.handle.net/10261/245492
Access Level:acceso abierto
Palabra clave:Aripiprazole
Metabolism
Olanzapine
Pharmacogenetics
Pharmacokinetics
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics
title Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics
spellingShingle Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics
Koller, Dora
Aripiprazole
Metabolism
Olanzapine
Pharmacogenetics
Pharmacokinetics
title_short Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics
title_full Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics
title_fullStr Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics
title_full_unstemmed Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics
title_sort Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics
dc.creator.none.fl_str_mv Koller, Dora
Almenara, Susana
Mejía, Gina
Saiz-Rodríguez, Miriam
Zubiaur, Pablo
Román, Manuel
Ochoa, Dolores
Navares-Gómez, Marcos
Santos-Molina, Elena
Pintos-Sánchez, Elena
Abad-Santos, Francisco
author Koller, Dora
author_facet Koller, Dora
Almenara, Susana
Mejía, Gina
Saiz-Rodríguez, Miriam
Zubiaur, Pablo
Román, Manuel
Ochoa, Dolores
Navares-Gómez, Marcos
Santos-Molina, Elena
Pintos-Sánchez, Elena
Abad-Santos, Francisco
author_role author
author2 Almenara, Susana
Mejía, Gina
Saiz-Rodríguez, Miriam
Zubiaur, Pablo
Román, Manuel
Ochoa, Dolores
Navares-Gómez, Marcos
Santos-Molina, Elena
Pintos-Sánchez, Elena
Abad-Santos, Francisco
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Comunidad de Madrid
Koller, Dora [0000-0002-0415-0466]
Abad-Santos, Francisco [0000-0002-6519-8885]
dc.subject.none.fl_str_mv Aripiprazole
Metabolism
Olanzapine
Pharmacogenetics
Pharmacokinetics
topic Aripiprazole
Metabolism
Olanzapine
Pharmacogenetics
Pharmacokinetics
description [Introduction] Aripiprazole and olanzapine are atypical antipsychotics. Both drugs can induce metabolic changes; however, the metabolic side effects produced by aripiprazole are more benign. The aim of the study was to evaluate if aripiprazole and olanzapine alter prolactin levels, lipid and glucose metabolism and hepatic, haematological, thyroid and renal function. [Methods] Twenty-four healthy volunteers received a daily oral dose of 10 mg aripiprazole and 5 mg olanzapine tablets for 5 days in a crossover randomised clinical trial and were genotyped for 51 polymorphisms in 18 genes by qPCR. Drug plasma concentrations were measured by LC–MS. The biochemical and haematological analyses were performed by enzymatic methods. [Results] Olanzapine induced hyperprolactinaemia but aripiprazole did not. Dopamine D3 receptor (DRD3) Ser/Gly and ATP binding cassette subfamily B member 1 (ABCB1) rs10280101, rs12720067 and rs11983225 polymorphisms and cytochrome P450 3A (CYP3A) phenotype had an impact on plasma prolactin levels. C-peptide concentrations were higher after aripiprazole administration and were influenced by catechol-O-methyltransferase (COMT) rs4680 and rs13306278 polymorphisms. Olanzapine and the UDP glucuronosyltransferase family 1 member A1 (UGT1A1) rs887829 polymorphism were associated with elevated glucose levels. CYP3A poor metabolizers had increased insulin levels. Volunteers’ weight decreased significantly during aripiprazole treatment and a tendency for weight gain was observed during olanzapine treatment. Triglyceride concentrations decreased as a result of olanzapine and aripiprazole treatment, and varied on the basis of CYP3A phenotypes and the apolipoprotein C-III (APOC3) rs4520 genotype. Cholesterol levels were also decreased and depended on 5-hydroxytryptamine receptor 2A (HTR2A) rs6314 polymorphism. All hepatic enzymes, platelet and albumin levels, and prothrombin time were altered during both treatments. Additionally, olanzapine reduced the leucocyte count, aripiprazole increased free T4 and both decreased uric acid concentrations. [Conclusions] Short-term treatment with aripiprazole and olanzapine had a significant influence on the metabolic parameters. However, it seems that aripiprazole provokes less severe metabolic changes.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
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/10261/245492
url http://hdl.handle.net/10261/245492
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/H2020/721236
PEJ-2018-TL/BMD-11080
Koller, Dora; Almenara, Susana; Mejía, Gina; Saiz-Rodríguez, Miriam; Zubiaur, Pablo; Román, Manuel; Ochoa, Dolores; Navares-Gómez, Marcos; Santos-Molina, Elena; Pintos-Sánchez, Elena; Abad-Santos, Francisco. (2021) "Dataset related to article: Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics [Dataset]", http://dx.doi.org/10.20350/digitalCSIC/13930
https://doi.org/10.1007/s12325-020-01566-w
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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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spelling Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with PharmacogeneticsKoller, DoraAlmenara, SusanaMejía, GinaSaiz-Rodríguez, MiriamZubiaur, PabloRomán, ManuelOchoa, DoloresNavares-Gómez, MarcosSantos-Molina, ElenaPintos-Sánchez, ElenaAbad-Santos, FranciscoAripiprazoleMetabolismOlanzapinePharmacogeneticsPharmacokinetics[Introduction] Aripiprazole and olanzapine are atypical antipsychotics. Both drugs can induce metabolic changes; however, the metabolic side effects produced by aripiprazole are more benign. The aim of the study was to evaluate if aripiprazole and olanzapine alter prolactin levels, lipid and glucose metabolism and hepatic, haematological, thyroid and renal function. [Methods] Twenty-four healthy volunteers received a daily oral dose of 10 mg aripiprazole and 5 mg olanzapine tablets for 5 days in a crossover randomised clinical trial and were genotyped for 51 polymorphisms in 18 genes by qPCR. Drug plasma concentrations were measured by LC–MS. The biochemical and haematological analyses were performed by enzymatic methods. [Results] Olanzapine induced hyperprolactinaemia but aripiprazole did not. Dopamine D3 receptor (DRD3) Ser/Gly and ATP binding cassette subfamily B member 1 (ABCB1) rs10280101, rs12720067 and rs11983225 polymorphisms and cytochrome P450 3A (CYP3A) phenotype had an impact on plasma prolactin levels. C-peptide concentrations were higher after aripiprazole administration and were influenced by catechol-O-methyltransferase (COMT) rs4680 and rs13306278 polymorphisms. Olanzapine and the UDP glucuronosyltransferase family 1 member A1 (UGT1A1) rs887829 polymorphism were associated with elevated glucose levels. CYP3A poor metabolizers had increased insulin levels. Volunteers’ weight decreased significantly during aripiprazole treatment and a tendency for weight gain was observed during olanzapine treatment. Triglyceride concentrations decreased as a result of olanzapine and aripiprazole treatment, and varied on the basis of CYP3A phenotypes and the apolipoprotein C-III (APOC3) rs4520 genotype. Cholesterol levels were also decreased and depended on 5-hydroxytryptamine receptor 2A (HTR2A) rs6314 polymorphism. All hepatic enzymes, platelet and albumin levels, and prothrombin time were altered during both treatments. Additionally, olanzapine reduced the leucocyte count, aripiprazole increased free T4 and both decreased uric acid concentrations. [Conclusions] Short-term treatment with aripiprazole and olanzapine had a significant influence on the metabolic parameters. However, it seems that aripiprazole provokes less severe metabolic changes.The study and DK were financed by the H2020 Marie Sklodowska-Curie Innovative Training Network 721236 grant. MN is co-financed by “Consejería de Educación, Juventud y Deporte” PEJ-2018-TL/BMD-11080 grant from “Comunidad de Madrid” and “Fondo Social Europeo”. No Rapid Service Fee was received by the journal for the publication of this article.Peer reviewedSpringer NatureEuropean CommissionComunidad de MadridKoller, Dora [0000-0002-0415-0466]Abad-Santos, Francisco [0000-0002-6519-8885]202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/245492reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/721236PEJ-2018-TL/BMD-11080Koller, Dora; Almenara, Susana; Mejía, Gina; Saiz-Rodríguez, Miriam; Zubiaur, Pablo; Román, Manuel; Ochoa, Dolores; Navares-Gómez, Marcos; Santos-Molina, Elena; Pintos-Sánchez, Elena; Abad-Santos, Francisco. (2021) "Dataset related to article: Metabolic Effects of Aripiprazole and Olanzapine Multiple-Dose Treatment in a Randomised Crossover Clinical Trial in Healthy Volunteers: Association with Pharmacogenetics [Dataset]", http://dx.doi.org/10.20350/digitalCSIC/13930https://doi.org/10.1007/s12325-020-01566-wNoinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2454922026-05-22T06:33:51Z
score 15,81155

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