Francisco José Toja-Camba , Gonzalo Hermelo Vidal , María Vidal-Millares , María José Durán-Maseda , Alicia Rial-Pérez , Olalla Maroñas , Angel Carracedo , Ana Estany Gestal , Francisco Cajade-Pascual , Irene Zarra-Ferro , Anxo Fernández-Ferreiro , Cristina Mondelo-García
{"title":"接受长效治疗的患者体内 CYP2D6 和 CYP3A4 多态性对阿立哌唑和脱氢阿立哌唑浓度的影响。","authors":"Francisco José Toja-Camba , Gonzalo Hermelo Vidal , María Vidal-Millares , María José Durán-Maseda , Alicia Rial-Pérez , Olalla Maroñas , Angel Carracedo , Ana Estany Gestal , Francisco Cajade-Pascual , Irene Zarra-Ferro , Anxo Fernández-Ferreiro , Cristina Mondelo-García","doi":"10.1016/j.pnpbp.2024.111134","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p><p>This study aims to evaluate the effect of <em>CYP2D6</em> and <em>CYP3A4</em> 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.</p><p>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.</p><p>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.</p><p>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.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"135 ","pages":"Article 111134"},"PeriodicalIF":5.3000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0278584624002021/pdfft?md5=9c9a401d8b91f191f0a0a107d16ab897&pid=1-s2.0-S0278584624002021-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Role of CYP2D6 and CYP3A4 polymorphisms on aripiprazole and dehydroaripiprazole concentrations in patients undergoing long-acting treatment\",\"authors\":\"Francisco José Toja-Camba , Gonzalo Hermelo Vidal , María Vidal-Millares , María José Durán-Maseda , Alicia Rial-Pérez , Olalla Maroñas , Angel Carracedo , Ana Estany Gestal , Francisco Cajade-Pascual , Irene Zarra-Ferro , Anxo Fernández-Ferreiro , Cristina Mondelo-García\",\"doi\":\"10.1016/j.pnpbp.2024.111134\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p><p>This study aims to evaluate the effect of <em>CYP2D6</em> and <em>CYP3A4</em> 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.</p><p>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.</p><p>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.</p><p>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.</p></div>\",\"PeriodicalId\":54549,\"journal\":{\"name\":\"Progress in Neuro-Psychopharmacology & Biological Psychiatry\",\"volume\":\"135 \",\"pages\":\"Article 111134\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0278584624002021/pdfft?md5=9c9a401d8b91f191f0a0a107d16ab897&pid=1-s2.0-S0278584624002021-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Progress in Neuro-Psychopharmacology & Biological Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0278584624002021\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0278584624002021","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Role of CYP2D6 and CYP3A4 polymorphisms on aripiprazole and dehydroaripiprazole concentrations in patients undergoing long-acting treatment
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.
期刊介绍：
Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject.
Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.
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