Influence of CYP2D6*3, CYP2D6*9 and CYP2D6*14 polymorphism on donepezil metabolism among dementia patient in memory clinic, Hospital Kuala Lumpur

In Malaysia, the Alzheimer's disease (AD) approximately reached more than 500 000 people in 2050. Donepezil is one of Acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD) that metabolized by CYP2D6 isoenzyme. The isoenzyme was found to be highly polymorphic which may affect the metabolism of donepezil. The main objectives of this research is to identify genotype-phenotype correlation and clinical implication of Donepezil metabolism in dementia due to influence of polymorphism CYP2D6*3, CYP2D6*9 and CYP2D6* 14. This was a retrospective study of 21 Malaysian diagnosed with dementia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth (DSM-IV) and Fifth Edition (DSM-V). Patients were treated with 5-10mg/daily of Donepezil for a year. Cognitive and functional statuses were evaluated using Neuropsychiatric Inventory (NPJ), Instrumental Activity of Daily Living (IADL) and Mini Mental State Examination (MMSE). Pharmacokinetic parameters, drug interaction, drug-related side effects and tolerability status were also evaluated. The analysis identifying CYP2D6 polymorphism was performed in double blinded fashion. After a year follow-up, 21 of 54 patients were responders and succeeded until genotyping procedure completed. The mean age of our population are 76.14±7.492 years (p =0.513) showed that the result is normally distributed. Almost half of the population had Mixed Dementia (47.6%) which consists of Alzheimer's disease and vascular dementia. 50% of the population is extensive metabolizer (EM). The result also showed the MMSE score changes from upon treatment until a year after treatment is -1.0952±3 .3 75 with normally distributed data according to Shapiro Wilk Test (p = 0.343). The MMSE value changes among CYP2D6-UM showed changes from - 7 to 7 (n=6).