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CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia
PURPOSE: Donepezil, a drug frequently used to treat dementia, is mainly metabolized by cytochrome P450 2D6 (CYP2D6). This study investigated the relationships between CYP2D6 genotype and activity scores as well as predicted phenotype of plasma donepezil concentrations in 86 Thai dementia participant...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649971/ https://www.ncbi.nlm.nih.gov/pubmed/33177862 http://dx.doi.org/10.2147/PGPM.S276230 |
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author | Chamnanphon, Monpat Wainipitapong, Sorawit Wiwattarangkul, Teeravut Chuchuen, Phenphichcha Nissaipan, Kunathip Phaisal, Weeraya Tangwongchai, Sookjaroen Sukasem, Chonlaphat Wittayalertpanya, Supeecha Gaedigk, Andrea Aniwattanapong, Daruj Chariyavilaskul, Pajaree |
author_facet | Chamnanphon, Monpat Wainipitapong, Sorawit Wiwattarangkul, Teeravut Chuchuen, Phenphichcha Nissaipan, Kunathip Phaisal, Weeraya Tangwongchai, Sookjaroen Sukasem, Chonlaphat Wittayalertpanya, Supeecha Gaedigk, Andrea Aniwattanapong, Daruj Chariyavilaskul, Pajaree |
author_sort | Chamnanphon, Monpat |
collection | PubMed |
description | PURPOSE: Donepezil, a drug frequently used to treat dementia, is mainly metabolized by cytochrome P450 2D6 (CYP2D6). This study investigated the relationships between CYP2D6 genotype and activity scores as well as predicted phenotype of plasma donepezil concentrations in 86 Thai dementia participants. MATERIALS AND METHODS: CYP2D6 was genotyped using bead-chip technology (Luminex xTAG(®) v.3). Steady-state trough plasma donepezil concentrations were measured using high-performance liquid chromatography. RESULTS: Sixteen genotypes were found but the most frequent genotypes detected among our participants were CYP2D6*10/*10 (27.9%) and *1/*10 (26.7%). One-third of the participants had an activity score of 1.25 which predicted that they were normal metabolizers. The overall median (interquartile range) of plasma donepezil concentration was 51.20 (32.59–87.24) ng/mL. Normal metabolizers (NMs) had lower plasma donepezil concentrations compared to intermediate metabolizers (IMs) (41.15 (28.44–67.65) ng/mL vs 61.95 (35.25–97.00) ng/mL). Multivariate analysis showed that CYP2D6 activity score (r(2) = 0.50) and the predicted phenotype (independent of dose) could predict the plasma donepezil concentration (r(2) = 0.49). CONCLUSION: Plasma donepezil concentration in NMs was lower compared to IMs. Additional studies with larger sample size and use of next-generation sequencing as well as its outcomes are warranted to confirm the benefit of using pharmacogenetic-guided treatment for donepezil. |
format | Online Article Text |
id | pubmed-7649971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-76499712020-11-10 CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia Chamnanphon, Monpat Wainipitapong, Sorawit Wiwattarangkul, Teeravut Chuchuen, Phenphichcha Nissaipan, Kunathip Phaisal, Weeraya Tangwongchai, Sookjaroen Sukasem, Chonlaphat Wittayalertpanya, Supeecha Gaedigk, Andrea Aniwattanapong, Daruj Chariyavilaskul, Pajaree Pharmgenomics Pers Med Original Research PURPOSE: Donepezil, a drug frequently used to treat dementia, is mainly metabolized by cytochrome P450 2D6 (CYP2D6). This study investigated the relationships between CYP2D6 genotype and activity scores as well as predicted phenotype of plasma donepezil concentrations in 86 Thai dementia participants. MATERIALS AND METHODS: CYP2D6 was genotyped using bead-chip technology (Luminex xTAG(®) v.3). Steady-state trough plasma donepezil concentrations were measured using high-performance liquid chromatography. RESULTS: Sixteen genotypes were found but the most frequent genotypes detected among our participants were CYP2D6*10/*10 (27.9%) and *1/*10 (26.7%). One-third of the participants had an activity score of 1.25 which predicted that they were normal metabolizers. The overall median (interquartile range) of plasma donepezil concentration was 51.20 (32.59–87.24) ng/mL. Normal metabolizers (NMs) had lower plasma donepezil concentrations compared to intermediate metabolizers (IMs) (41.15 (28.44–67.65) ng/mL vs 61.95 (35.25–97.00) ng/mL). Multivariate analysis showed that CYP2D6 activity score (r(2) = 0.50) and the predicted phenotype (independent of dose) could predict the plasma donepezil concentration (r(2) = 0.49). CONCLUSION: Plasma donepezil concentration in NMs was lower compared to IMs. Additional studies with larger sample size and use of next-generation sequencing as well as its outcomes are warranted to confirm the benefit of using pharmacogenetic-guided treatment for donepezil. Dove 2020-11-02 /pmc/articles/PMC7649971/ /pubmed/33177862 http://dx.doi.org/10.2147/PGPM.S276230 Text en © 2020 Chamnanphon et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Chamnanphon, Monpat Wainipitapong, Sorawit Wiwattarangkul, Teeravut Chuchuen, Phenphichcha Nissaipan, Kunathip Phaisal, Weeraya Tangwongchai, Sookjaroen Sukasem, Chonlaphat Wittayalertpanya, Supeecha Gaedigk, Andrea Aniwattanapong, Daruj Chariyavilaskul, Pajaree CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia |
title | CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia |
title_full | CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia |
title_fullStr | CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia |
title_full_unstemmed | CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia |
title_short | CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia |
title_sort | cyp2d6 predicts plasma donepezil concentrations in a cohort of thai patients with mild to moderate dementia |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649971/ https://www.ncbi.nlm.nih.gov/pubmed/33177862 http://dx.doi.org/10.2147/PGPM.S276230 |
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