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dc.contributor.authorSaiz-Rodríguez, Miriam
dc.contributor.authorAlmenara, Susana
dc.contributor.authorNavares-Gómez, Marcos
dc.contributor.authorOchoa, Dolores
dc.contributor.authorRomán, Manuel
dc.contributor.authorZubiaur, Pablo
dc.contributor.authorKoller, Dora
dc.contributor.authorSantos, María
dc.contributor.authorMejía, Gina
dc.contributor.authorBorobia, Alberto M
dc.contributor.authorRodriguez Antona, Cristina 
dc.contributor.authorAbad-Santos, Francisco
dc.date.accessioned2020-04-30T14:34:44Z
dc.date.available2020-04-30T14:34:44Z
dc.date.issued2020-04-22
dc.identifier.citationBiomedicines. 2020;8(4). pii: E94.es_ES
dc.identifier.issn2227-9059es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9849
dc.description.abstractSeveral cytochrome P450 (CYP) CYP3A polymorphisms were associated with reduced enzyme function. We aimed to evaluate the influence of these alleles on the pharmacokinetic parameters (PK) of several CYP3A substrates. We included 251 healthy volunteers who received a single dose of ambrisentan, atorvastatin, imatinib, aripiprazole, fentanyl, amlodipine, donepezil, olanzapine, fesoterodine, or quetiapine. The volunteers were genotyped for CYP3A4 and CYP3A5 polymorphisms by qPCR. To compare the PK across studies, measurements were corrected by the mean of each parameter for every drug and were logarithmically transformed. Neither CYP3A phenotype nor individual CYP3A4 or CYP3A5 polymorphisms were significantly associated with differences in PK. However, regarding the substrates that are exclusively metabolized by CYP3A, we observed a higher normalized AUC (p = 0.099) and a tendency of lower normalized Cl (p = 0.069) in CYP3A4 mutated allele carriers what was associated with diminished drug metabolism capacity. CYP3A4 polymorphisms did not show a pronounced influence on PK of the analysed drugs. If so, their impact could be detectable in a very small percentage of subjects. Although there are few subjects carrying CYP3A4 double mutations, the effect in those might be relevant, especially due to the majority of subjects lacking the CYP3A5 enzyme. In heterozygous subjects, the consequence might be less noticeable due to the high inducible potential of the CYP3A4 enzyme.es_ES
dc.description.sponsorshipF.A.S. and D.O. have been consultants or investigators in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Cinfa, FAES, Farmalíder, Ferrer, GlaxoSmithKline, Galenicum,Gilead, Italfarmaco, Janssen-Cilag, Kern, Normon, Novartis, Servier, Silverpharma, Teva and Zambon. M.N.G isco-financed by the European Social Fund and the Youth European Initiative, grant number PEJ-2018-TL/BMD-11080.D.K. is co-financed by the H2020 Marie Sklodowska-Curie Innovative Training Network 721236 grant.es_ES
dc.language.isoenges_ES
dc.publisherMPDIes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectCYP3A4es_ES
dc.subjectCYP3A5es_ES
dc.subjectpharmacokineticses_ES
dc.titleEffect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrateses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID32331352es_ES
dc.format.volume8es_ES
dc.format.number4es_ES
dc.format.page94es_ES
dc.identifier.doi10.3390/biomedicines8040094es_ES
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.3390/biomedicines8040094.es_ES
dc.identifier.journalBiomedicineses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Cáncer Endocrino Hereditarioes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional