Pharmacogenetics of Donepezil and Memantine in Healthy Subjects.

Alzheimer NMDA receptor antagonist anticholinergic drugs personalized medicine pharmacogenetic array pharmacogenomics pharmacokinetics

Journal

Journal of personalized medicine
ISSN: 2075-4426
Titre abrégé: J Pers Med
Pays: Switzerland
ID NLM: 101602269

Informations de publication

Date de publication:
13 May 2022
Historique:
received: 12 04 2022
revised: 08 05 2022
accepted: 11 05 2022
entrez: 28 5 2022
pubmed: 29 5 2022
medline: 29 5 2022
Statut: epublish

Résumé

Donepezil and memantine are the most common drugs used for Alzheimer's disease. Their low effectiveness could partly be explained by genetic factors. Thus, we aim to identify Single Nucleotide Polymorphisms (SNPs) associated with pharmacokinetics, pharmacodynamics, and the safety of donepezil and memantine. For this regard, 25 volunteers enrolled in a bioequivalence clinical trial were genotyped for 67 SNPs in 21 genes with a ThermoFisher QuantStudio 12K Flex OpenArray. The statistical strategy included a univariate analysis that analyzed the association of these SNPs with pharmacokinetic parameters or the development of adverse drug reactions (ADRs) followed by a Bonferroni-corrected multivariate regression. Statistical analyses were performed with SPSS software v.21 and R commander (version v3.6.3). In the univariate analysis, fourteen and sixteen SNPs showed a significant association with memantine's and donepezil's pharmacokinetic parameters, respectively. Rs20417 (

Identifiants

pubmed: 35629210
pii: jpm12050788
doi: 10.3390/jpm12050788
pmc: PMC9145014
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Instituto de Salud Carlos III
ID : ICI20/00131
Organisme : CIBERehd
ID : IMPaCT, IMP/00009

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Auteurs

María C Ovejero-Benito (MC)

Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, Spain.

Dolores Ochoa (D)

Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, Spain.
Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain.
Unidad de Investigación Clínica y Ensayos Clínicos (UICEC), Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Research Network), 28006 Madrid, Spain.

Teresa Enrique-Benedito (T)

Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, Spain.

Miriam Del Peso-Casado (M)

Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, Spain.

Pablo Zubiaur (P)

Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, Spain.
Unidad de Investigación Clínica y Ensayos Clínicos (UICEC), Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Research Network), 28006 Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain.

Marcos Navares (M)

Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, Spain.

Manuel Román (M)

Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, Spain.
Unidad de Investigación Clínica y Ensayos Clínicos (UICEC), Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Research Network), 28006 Madrid, Spain.

Francisco Abad-Santos (F)

Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, Spain.
Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain.
Unidad de Investigación Clínica y Ensayos Clínicos (UICEC), Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Research Network), 28006 Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Instituto Teófilo Hernando, 28029 Madrid, Spain.

Classifications MeSH