AUTHOR=Lu Jin , Wang Xiuzhe , Wan Lili , Fu Jianliang , Huo Yan , Zhao Yuwu , Guo Cheng 

TITLE=Gene Polymorphisms Affecting the Pharmacokinetics and Pharmacodynamics of Donepezil Efficacy

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00934

DOI=10.3389/fphar.2020.00934

ISSN=1663-9812

ABSTRACT=Donepezil (DNP) is the first-line drug used for Alzheimer’s disease (AD),

however, the therapeutic response rate of patients to DNP varies from 20%-60%, the main reason for the large differences in the clinical efficiency of DNP therapy are closely related to genetic factors, some of which are pharmacokinetics(PK)-related genes while others are pharmacodynamics(PD)-related genes. Thus much emphasis has been put on the investigation of an association between the related PK and PD gene polymorphisms and the therapeutic response of DNP, but a consistent view does not yet exist. In this review, we summarize recent findings regarding the genetic factors influenced the clinical efficacy of DNP, where larger individual differences are seen as a consequence of polymorphic alleles with CYP2D6, CY3A4, CY3A5,APOE, ABCA1, ABCB1,ESR1, BCHE, PON-1, CHRNA7 and CHAT.

We also discuss possible strategies for the evaluation of clilincal efficacy of DNP, with a specifical focus on possible biomarkers of PK / PD, and reflect the perspectives and the limitations of the field, which will also be beneficial to understand the multiple mechanisms of DNP therapy to AD.