Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations
Abstract 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 treatm...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84192-8 |
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| author | Francisco José Toja-Camba María Vidal-Millares María José Durán-Maseda Gonzalo Hermelo-Vidal Ángel Carracedo Olalla Maroñas Luis Ramudo-Cela Irene Zarra-Ferro Anxo Fernández-Ferreiro Cristina Mondelo-García |
| author_facet | Francisco José Toja-Camba María Vidal-Millares María José Durán-Maseda Gonzalo Hermelo-Vidal Ángel Carracedo Olalla Maroñas Luis Ramudo-Cela Irene Zarra-Ferro Anxo Fernández-Ferreiro Cristina Mondelo-García |
| author_sort | Francisco José Toja-Camba |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-2862ea1720404cfabacaefc4ac220d89 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2862ea1720404cfabacaefc4ac220d892025-01-12T12:23:25ZengNature PortfolioScientific Reports2045-23222025-01-011511710.1038/s41598-024-84192-8Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrationsFrancisco José Toja-Camba0María Vidal-Millares1María José Durán-Maseda2Gonzalo Hermelo-Vidal3Ángel Carracedo4Olalla Maroñas5Luis Ramudo-Cela6Irene Zarra-Ferro7Anxo Fernández-Ferreiro8Cristina Mondelo-García9Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS)Psychiatry Department, University Clinical Hospital of Santiago de CompostelaPsychiatry Department, University Clinical Hospital of Santiago de CompostelaFarmaCHUSLab Group, Health Research Institute of Santiago de Compostela (IDIS)Genetics Group, Health Research Institute of Santiago de Compostela (IDIS)Galician Foundation of Genomic Medicine, Foundation of Health Research Institute of Santiago de Compostela (FIDIS), SERGASPharmacy Department, University Clinical Hospital A Coruña (CHUAC)Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS)Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS)Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS)Abstract 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.https://doi.org/10.1038/s41598-024-84192-8P-glycoproteinAripiprazoleDehydroaripiprazolePharmacogeneticsPharmacokinetics |
| spellingShingle | Francisco José Toja-Camba María Vidal-Millares María José Durán-Maseda Gonzalo Hermelo-Vidal Ángel Carracedo Olalla Maroñas Luis Ramudo-Cela Irene Zarra-Ferro Anxo Fernández-Ferreiro Cristina Mondelo-García Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations Scientific Reports P-glycoprotein Aripiprazole Dehydroaripiprazole Pharmacogenetics Pharmacokinetics |
| title | Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations |
| title_full | Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations |
| title_fullStr | Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations |
| title_full_unstemmed | Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations |
| title_short | Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations |
| title_sort | influence of abcb1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations |
| topic | P-glycoprotein Aripiprazole Dehydroaripiprazole Pharmacogenetics Pharmacokinetics |
| url | https://doi.org/10.1038/s41598-024-84192-8 |
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