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

ACCESS DATA

Publications

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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Dataset Information

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

Purpose

Materials and methods

Results

Conclusion

Publications

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

Similar Datasets

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