Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms

Article type: Research Article

Authors: Miranda, Luís F.J.R.^a | Gomes, Karina B.^b | Tito, Pedro A.L.^e | Silveira, Josianne N.^b | Pianetti, Gerson A.^b | Byrro, Ricardo M.D.^b | Peles, Patrícia R.H.^c | Pereira, Fernando H.^a | Santos, Thiago R.^d | Assini, Arthur G.^b | Ribeiro, Valéria V.^b | Moraes, Edgar N.^{a; f} | Caramelli, Paulo^{a; c; *}

Affiliations: [a] Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [b] Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [c] Serviço de Neurologia do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [d] Instituto de Ciências Exatas da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [e] Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [f] Serviço de Geriatria do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil

Correspondence: [*] Correspondence to: Paulo Caramelli, MD, PhD, Departamento de Clínica Médica, Faculdade de Medicina da UFMG, Av. Prof. Alfredo Balena, 190 – Room 246, 30130-100, Belo Horizonte (MG), Brazil. Tel./Fax: +55 31 3409 9746; E-mail: [email protected].

Abstract: The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer’s disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥–1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

Keywords: Alzheimer’s disease, APOE, CYP2D6, donepezil, genetics, naturalistic study

DOI: 10.3233/JAD-160164

Journal: Journal of Alzheimer's Disease, vol. 55, no. 2, pp. 539-549, 2017