Dataset Information

CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia.

ABSTRACT: 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 (r2 = 0.50) and the predicted phenotype (independent of dose) could predict the plasma donepezil concentration (r2 = 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.

SUBMITTER: Chamnanphon M

PROVIDER: S-EPMC7649971 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia.

Chamnanphon Monpat M Wainipitapong Sorawit S Wiwattarangkul Teeravut T Chuchuen Phenphichcha P Nissaipan Kunathip K Phaisal Weeraya W Tangwongchai Sookjaroen S Sukasem Chonlaphat C Wittayalertpanya Supeecha S Gaedigk Andrea A Aniwattanapong Daruj D Chariyavilaskul Pajaree P

Pharmacogenomics and personalized medicine 20201102

<h4>Purpose</h4>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.<h4>Materials and methods</h4>CYP2D6 was genotyped using bead-chip technology (Luminex xTAG<sup>®</sup> v.3). Steady-state trough plasma donepezil concentrations were measured using high-perf ...[more]

PMID: 33177862

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Project description:BACKGROUND: The management of mild to moderate dementia presents complex and evolving challenges. Practising physicians are often uncertain about the appropriate approaches to issues such as the disclosure of the diagnosis, driving and caregiver support. In this article, we provide practical guidance on management based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. METHODS: We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of mild to moderate stages of Alzheimer disease and other forms of dementia. Recommendations based on the literature review were drafted and voted on. Consensus required 80% or more agreement by participants. Subsequent to the conference, we searched for additional articles published from January 2006 to April 2008 using the same major keywords and secondary search terms. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. RESULTS: We identified 1615 articles, of which 954 were selected for further study. From a synthesis of the evidence in these studies, we made 48 recommendations for the management of mild to moderate dementia (28) and dementia with a cerebrovascular component (8) as well as recommendations for addressing ethical issues (e.g., disclosure of the diagnosis) (12). The updated literature review did not change these recommendations. In brief, patients and their families should be informed of the diagnosis. Although the specifics of managing comorbid conditions might require modification, standards of care and treatment targets would not change because of a mild dementia. The use of medications with anticholinergic effects should be minimized. There should be proactive planning for driving cessation, since this will be required at some point in the course of progressive dementia. The patient's ability to drive should be determined primarily on the basis of his or her functional abilities. An important aspect of care is supporting the patient's primary caregiver. INTERPRETATION: Much has been learned about the care of patients with mild to moderate dementia and the support of their primary caregivers. There is a pressing need for the development, and dissemination, of collaborative systems of care.

Project description:BackgroundPractising physicians frequently seek advice on the most effective interventions for dementia. In this article, we provide practical guidance on nonpharmacologic and pharmacologic interventions for the management of mild to moderate dementia based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia.MethodsWe developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of mild to moderate stages of Alzheimer disease and other forms of dementia. Recommendations based on the literature review were drafted and voted on. Consensus required 80% or more agreement by participants. Subsequent to the conference, we searched for additional articles published from January 2006 to April 2008 using the same major keywords and secondary search terms. We graded the strength of the evidence using the criteria of the Canadian Task Force on Preventive Health Care.ResultsWe identified 1615 articles, of which 954 were selected for further study. From a synthesis of the evidence in these studies, we made 48 recommendations for the management of mild to moderate dementia (28) and dementia with a cerebrovascular component (8) as well as recommendations for addressing ethical issues (e.g., disclosure of the diagnosis) (12). The updated literature review did not change these recommendations. An exercise program is recommended for patients with mild to moderate dementia. Physicians should decide whether to prescribe a cholinesterase inhibitor on an individual basis, balancing anticipated benefits with the potential for harm. For mild mood and behavioural concerns, nonpharmacologic approaches should be considered first.InterpretationAlthough the available therapies for dementia can help with the management of symptoms, there is a need to develop more effective interventions.

Dataset Information

CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia.

Publications

CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia.

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