Authors: Federica Varsaldi Gianluca Miglio Maria Gabriella Scordo MarjaLiisa Dahl Laura Maria Villa Aldo Biolcati Grazia Lombardi
Publish Date: 2006/07/15
Volume: 62, Issue: 9, Pages: 721-726
Abstract
The aims of this study were to evaluate the impact of the CYP2D6 polymorphism on both the steadystate plasma concentrations Cp and the clinical outcome of donepezil a selective acetylcholinesterase inhibitor used in the treatment of Alzheimer’s disease ADFortytwo patients of Caucasian ethnicity affected by probable AD were included in the study All had been receiving therapy with donepezil for at least 3 months 31 patients with 5 mg/day and 11 patients with 10 mg/day The CYP2D6 genotype was analysed and donepezil Cp was measured by using highperformance liquid chromatographyOn the basis of their CYP2D6 genotype 30 patients could be classified as homozygous extensive metabolizers EM 10 as heterozygous EM and 2 as ultrarapid metabolizers UM No poor metabolizer was found The dose and body weightcorrected median donepezil Cp were slightly though not significantly lower in homozygous than in heterozygous EM 033 vs 041 ng/ml/mg/kg respectively The latter group consistently showed a better clinical response to treatment as measured by change in MiniMental State Examination score median 140 vs −130 respectively UM patients had lower Cp than EM patients and showed no clinical improvementOur preliminary data suggest that the CYP2D6 polymorphism influences both donepezil metabolism and therapeutic outcome and that a knowledge of a patient’s CYP2D6 genotype together with donepezil concentration measurements might be useful in the context of improving the clinical efficacy of donepezil therapyThis study was supported by the Piedmont County Grants for Research Turin Italy by grants from SIF “Società Italiana di Farmacologia” Pfizer Italia Srl and Pfizer AB Sweden the Swedish Medical Society and the Swedish Research Council 2002–6475 We thank Dr Norio YasuiFurukori Hirosaki University School of Medicine Japan for the generous gift of donepezil and Prof Maurizio Rinaldi and Dr R Gindro DISCAFF Department University of Eastern Piedmont Italy for advice on statistical analysis The study protocol was approved by the Research Ethics Committee at the “Ospedale Maggiore della Carità” of Novara Italy in accordance with the ethical standards laid down in the Declaration of Helsinki
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