Impact of CYP2D6 and CYP3A4 genetic polymorphism on combined cholinesterase inhibitors and memantine treatment in mild to moderate Alzheimer's disease

Nirmal Sonali; Manjari Tripathi; Rajesh Sagar; Thirumurthy Velpandian; Vivekanandhan Subbiah

doi:10.1159/000350050

Impact of CYP2D6 and CYP3A4 genetic polymorphism on combined cholinesterase inhibitors and memantine treatment in mild to moderate Alzheimer's disease

Dement Geriatr Cogn Disord. 2014;37(1-2):58-70. doi: 10.1159/000350050. Epub 2013 Oct 3.

Authors

Nirmal Sonali¹, Manjari Tripathi, Rajesh Sagar, Thirumurthy Velpandian, Vivekanandhan Subbiah

Affiliation

¹ Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi, India.

PMID: 24107805
DOI: 10.1159/000350050

Abstract

Aim: The impact of CYP2D6 and CYP3A4 polymorphism on the steady-state plasma concentrations and therapeutic outcome of donepezil monotherapy and combination therapy in Alzheimer's disease (AD) patients.

Methods: A total of 38 patients for donepezil and 17 patients for donepezil and memantine therapy, aged ≥ 55 years, were recruited meeting inclusion and exclusion criteria. Polymerase chain reaction-restriction fragment length polymorphism was performed. The liquid chromatography-tandem mass spectrometry method was used for estimation of drug levels of donepezil and memantine.

Results: Significant allele frequency was observed for CYP2D6*3 polymorphism in patients on donepezil monotherapy and combination therapy. Significant allele frequency for CYP2D6*4 was observed in the patients on donepezil monotherapy.

Conclusion: CYP2D6 polymorphism, though not significant, might partially be involved in the plasma concentration of AD drug.

MeSH terms

Aged
Alleles
Alzheimer Disease / drug therapy*
Alzheimer Disease / psychology
Cholinesterase Inhibitors / blood
Cholinesterase Inhibitors / therapeutic use*
Chromatography, High Pressure Liquid
Cognitive Dysfunction / drug therapy
Cognitive Dysfunction / psychology
Cytochrome P-450 CYP2D6 / genetics*
Cytochrome P-450 CYP3A / genetics*
DNA / genetics
Diagnostic and Statistical Manual of Mental Disorders
Donepezil
Dopamine Agents / blood
Dopamine Agents / therapeutic use*
Drug Therapy, Combination
Female
Genotype
Humans
Indans / blood
Indans / therapeutic use
India
Male
Memantine / blood
Memantine / therapeutic use*
Middle Aged
Neuropsychological Tests
Nootropic Agents / blood
Nootropic Agents / therapeutic use
Piperidines / blood
Piperidines / therapeutic use
Polymorphism, Genetic / genetics
Tandem Mass Spectrometry
Treatment Outcome

Substances

Cholinesterase Inhibitors
Dopamine Agents
Indans
Nootropic Agents
Piperidines
Donepezil
DNA
Cytochrome P-450 CYP2D6
Cytochrome P-450 CYP3A
CYP3A4 protein, human
Memantine