RT Journal Article
T1 Role of CYP2D6 and CYP3A4 polymorphisms on aripiprazole and dehydroaripiprazole concentrations in patients undergoing long-acting treatment
A1 Toja-Camba, Francisco José
A1 Hermelo Vidal, Gonzalo
A1 Vidal-Millares, María
A1 Durán-Maseda, María José
A1 Rial Pérez, Alicia
A1 Maroñas, Olalla
A1 Carracedo Álvarez, Ángel
A1 Estany Gestal, Ana
A1 Cajade-Pascual, Francisco
A1 Zarra Ferro, Irene
A1 Fernández Ferreiro, Anxo
A1 Mondelo García, Cristina
K1 Aripiprazole
K1 Dehydroaripiprazole
K1 CYP2D6
K1 CYP3A4
K1 Active moiety
AB 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.
PB Elsevier
YR 2024
FD 2024-09-03
LK https://hdl.handle.net/10347/39833
UL https://hdl.handle.net/10347/39833
LA eng
NO Toja-Camba, F. J., Vidal, G. H., Vidal-Millares, M., Durán-Maseda, M. J., Rial-Pérez, A., Maroñas, O., Carracedo, A., Gestal, A. E., Cajade-Pascual, F., Zarra-Ferro, I., Fernández-Ferreiro, A., & Mondelo-García, C. (2024). Role of CYP2D6 and CYP3A4 polymorphisms on aripiprazole and dehydroaripiprazole concentrations in patients undergoing long-acting treatment. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 13510.1016/j.pnpbp.2024.111134
NO This work was supported by the Spanish Society of Hospital Pharmacy through the Call for Aid to Work Groups 2021–2022 and Xunta de Galicia (GAIN) IN607A2023/04.
DS Minerva
RD 30 abr 2026