RT Journal Article
T1 Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations
A1 Toja Camba, Francisco José
A1 Vidal Millares, María
A1 Durán Maseda, María José
A1 Hermelo Vidal, Gonzalo
A1 Carracedo Álvarez, Ángel
A1 Maroñas, Olalla
A1 Ramudo Cela, Luis
A1 Zarra Ferro, Irene
A1 Fernández Ferreiro, Anxo
A1 Mondelo García, Cristina
K1 P-glycoprotein
K1 Aripiprazole
K1 Dehydroaripiprazole
K1 Pharmacogenetics
K1 Pharmacokinetics
AB Aripiprazole (ARI) is an atypical antipsychotic which is a substrate of P-glycoprotein (P-gp), a transmembrane glycoprotein that plays a crucial role in eliminating potentially harmful compounds from the organism. ARI once-monthly (AOM) is a long-acting injectable form which improves treatment compliance. Genetic polymorphisms in ABCB1 may lead to changes in P-gp function, leading to individual differences in drug disposition. The present study aims to determine how the different variants of the three most prevalent SNPs of the ABCB1 gene affect plasma concentrations of ARI, of its active metabolite dehydroaripiprazole (DHA) and ARI/DHA ratio in patients under AOM treatment. The metabolizing state of the two main aripiprazole metabolizing enzymes (CYP2D6 and CYP3A4) were considered to specifically study the effect of P-gp on plasma concentrations of the parent compound and its active metabolite. The study found a clear relationship between the genotypes found for the different ABCB1 SNPs and the ARI/DHA ratio. Specifically, patients with GG genotype in G2677T have almost twice the ratio compared to TT genotype. Similarly, this increase is also found in C3435T with 1.4-fold and in C1236T with 1.6-fold for the same genotypes. Regarding haplotypes, significant differences were obtained between CC-GG-CC and TT-TT-TT patients, with an 87.9% higher ratio in patients with the CC-GG-CC haplotype. There was a clear trend towards lower ARI concentrations and higher DHA concentrations when the presence of mutated T alleles increases. The ABCB1 gene could be a good partner along with CYP2D6 and CYP3A4 genotyping in conjunction with monitoring ARI plasma concentrations.
PB Nature
YR 2025
FD 2025-01-09
LK https://hdl.handle.net/10347/40992
UL https://hdl.handle.net/10347/40992
LA eng
NO Toja-Camba, F. J., Vidal-Millares, M., Durán-Maseda, M. J., Hermelo-Vidal, G., Carracedo, Á., Maroñas, O., Ramudo-Cela, L., Zarra-Ferro, I., Fernández-Ferreiro, A., & Mondelo-García, C. (2025). Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations. Scientific Reports, 15(1), 1521–1527. https://doi.org/10.1038/s41598-024-84192-8
NO This work was supported by the Spanish Society of Hospital Pharmacy through the Call for Aid to Work Groups 2021–2022 (SEFH21/22) and Xunta de Galicia (GAIN) IN607A2023/04.
DS Minerva
RD 28 abr 2026