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Role of CYP2D6 and CYP3A4 polymorphisms on aripiprazole and dehydroaripiprazole concentrations in patients undergoing long-acting treatment.
Toja-Camba, Francisco José; Vidal, Gonzalo Hermelo; Vidal-Millares, María; Durán-Maseda, María José; Rial-Pérez, Alicia; Maroñas, Olalla; Carracedo, Angel; Gestal, Ana Estany; Cajade-Pascual, Francisco; Zarra-Ferro, Irene; Fernández-Ferreiro, Anxo; Mondelo-García, Cristina.
Afiliación
  • Toja-Camba FJ; Pharmacy Department, University Clinical Hospital Santiago de Compostela (CHUS), Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Spain; Faculty of Pharmacy, University of Santiago de Compostela (USC), Spain.
  • Vidal GH; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Spain.
  • Vidal-Millares M; Psychiatry Department, University Clinical Hospital of Santiago de Compostela, Spain.
  • Durán-Maseda MJ; Psychiatry Department, University Clinical Hospital of Santiago de Compostela, Spain.
  • Rial-Pérez A; Psychiatry Department, University Clinical Hospital of Santiago de Compostela, Spain.
  • Maroñas O; Genomic Medicine Group, CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Galician Foundation of Genomic Medicine, Foundation of Health Research Institute of Santiago de Compostela (FIDIS), SERGAS, Santiago de Compostela, Spain; Centre for Biomedical Network Research
  • Carracedo A; Galician Foundation of Genomic Medicine, Foundation of Health Research Institute of Santiago de Compostela (FIDIS), SERGAS, Santiago de Compostela, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Carlos III Health Institute, Madrid, Spain; Pharmacogenomics and Drug discover
  • Gestal AE; Research Methodology Platform (IDIS), 15706 Santiago de Compostela, Spain.
  • Cajade-Pascual F; Pharmacy Department, University Clinical Hospital Santiago de Compostela (CHUS), Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Spain; Faculty of Pharmacy, University of Santiago de Compostela (USC), Spain.
  • Zarra-Ferro I; Pharmacy Department, University Clinical Hospital Santiago de Compostela (CHUS), Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Spain.
  • Fernández-Ferreiro A; Pharmacy Department, University Clinical Hospital Santiago de Compostela (CHUS), Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Spain. Electronic address: anxo.fernandez.ferreiro@usc.es.
  • Mondelo-García C; Pharmacy Department, University Clinical Hospital Santiago de Compostela (CHUS), Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Spain. Electronic address: cristina.mondelo.garcia@sergas.es.
Prog Neuropsychopharmacol Biol Psychiatry ; 135: 111134, 2024 Dec 20.
Article en En | MEDLINE | ID: mdl-39237024
ABSTRACT
Aripiprazole once-monthly (AOM) exhibits an important interindividual pharmacokinetic variability with significant implications for its clinical use. CYP2D6 and CYP3A4 highly contributes to this variability, as they metabolize aripiprazole (ARI) into its active metabolite, dehydroaripiprazole (DHA) and the latter into inactive metabolites. This study aims to evaluate the effect of CYP2D6 and CYP3A4 polymorphisms in combination and the presence of concomitant inducers and inhibitors of this cytochromes on ARI and DHA plasma concentrations in a real clinical setting. An observational study of a cohort of 74 Caucasian patients under AOM treatment was conducted. Regarding CYP2D6, higher concentrations were found for active moiety (ARI plus DHA) (AM) (67 %), ARI (67 %) and ARI/DHA ratio (77 %) for poor metabolizers (PMs) compared to normal metabolizers (NMs). No differences were found for DHA. PMs for both CYP2D6 and CYP3A4 showed a 58 % higher AM and 66 % higher plasma concentration for ARI compared with PMs for CYP2D6 and NMs for CYP3A4. In addition, PMs for both CYP2D6 and CYP3A4 have 45 % higher DHA concentrations than NMs for both cytochromes and 41 % more DHA than PMs for CYP2D6 and NMs for CYP3A4, suggesting a significant role of CYP3A4 in the elimination of DHA. Evaluating the effect of CYPD26 and CYP3A4 metabolizing state in combination on plasma concentrations of ARI, DHA and parent-to-metabolite ratio, considering concomitant treatments with inducers and inhibitor, could optimize therapy for patients under AOM treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antipsicóticos / Citocromo P-450 CYP2D6 / Citocromo P-450 CYP3A / Aripiprazol Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Prog Neuropsychopharmacol Biol Psychiatry Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antipsicóticos / Citocromo P-450 CYP2D6 / Citocromo P-450 CYP3A / Aripiprazol Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Prog Neuropsychopharmacol Biol Psychiatry Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido