Role of CYP2D6 and CYP3A4 polymorphisms on aripiprazole and dehydroaripiprazole concentrations in patients undergoing long-acting treatment

被引：0

作者：

Toja-Camba, Francisco Jose

Vidal, Gonzalo Hermelo ^{[2
]}

Vidal-Millares, Maria ^{[4
]}

Duran-Maseda, Maria Jose

Rial-Perez, Alicia

Maronas, Olalla ^{[5
,6
,7
,8
]}

Carracedo, Angel ^{[6
,7
,8
,9
]}

Gestal, Ana Estany ^{[10
]}

Cajade-Pascual, Francisco ^{[1
,2
,3
]}

Zarra-Ferro, Irene ^{[1
,2
]}

Fernandez-Ferreiro, Anxo ^{[1
,2
]}

Mondelo-Garcia, Cristina ^{[1
,2
]}

机构：

[1] Univ Clin Hosp Santiago de Compostela CHUS, Pharm Dept, Santiago De Compostela, Spain

[2] Hlth Res Inst Santiago de Compostela IDIS, Clin Pharmacol Grp, Santiago De Compostela, Spain

[3] Univ Santiago de Compostela USC, Fac Pharm, Santiago De Compostela, Spain

[4] Univ Clin Hosp Santiago de Compostela, Psychiat Dept, Santiago De Compostela, Spain

[5] Univ Santiago de Compostela, Genom Med Grp, CIMUS, Santiago De Compostela 15782, Spain

[6] SERGAS, Fdn Hlth Res Inst Santiago de Compostela FIDIS, Galician Fdn Genom Med, Santiago De Compostela, Spain

[7] Carlos III Hlth Inst, Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain

[8] Fdn Hlth Res Inst Santiago de Compostela FIDIS, Pharmacogen & Drug Discovery GenDeM, Dept Pathol, Santiago De Compostela, Galicia, Spain

[9] Hlth Res Inst Santiago de Compostela IDIS, Genet Grp, Santiago De Compostela, Spain

[10] Res Methodol Platform IDIS, Santiago De Compostela 15706, Spain

来源：

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY | 2024年 / 135卷

关键词：

Aripiprazole; Dehydroaripiprazole; Active moiety; CYP2D6; CYP3A4; SERUM CONCENTRATIONS; HIGH-FREQUENCY; SCHIZOPHRENIA; POLYMORPHISMS; HALOPERIDOL; RISPERIDONE; METABOLITE; GENOTYPE;

D O I：

10.1016/j.pnpbp.2024.111134

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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. Ms 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.

引用

页数：7