Cytochrome P450 2D6 Phenotyping in an Elderly Population With Dementia and Response to Galantamine in Dementia: A Pilot Study

Abstract

Background The cytochrome P450 (CYP) 2D6 enzyme is involved in the metabolism of many drugs used by the elderly population. Variations in its activity can lead to altered drug response. However, few studies on the activity of this enzyme system have enrolled the elderly population. Objective The goal of this pilot study was to assess the feasibility of in vivo phenotyping of CYP2D6 in an elderly population with dementia and to determine if part of the variability in response to treatment with galantamine is attributable to CYP2D6 phenotype. Methods Patients with dementia attending geriatric clinics and receiving galantamine treatment for at least 6 months were enrolled in this case-control study. CYP2D6 phenotype was determined by analysis of the urinary concentrations of the probe drug dextromethorphan and its primary metabolite dextrorphan after ingestion of 30 mg of dextromethorphan. Patients were classified as robust responders to galantamine if their cognitive testing, as measured by using scores on the Mini–Mental State Examination or Alzheimer's Disease Assessment Scale–Cognitive subscale, had not changed or had improved after 6 months of treatment. Results Forty-three patients (23 men, 20 women; mean age, 78.4 years; 98% white) underwent phenotyping. The mean number of concomitantly prescribed medications was 5.7, and 16 patients (37%) were receiving other CYP2D6 substrate or inhibitor drugs. The distribution of CYP2D6 phenotype was similar to that seen in other white populations. There was no correlation between the phenotypic metabolic ratio and age, the number of routinely taken medications, whether patients were receiving other prescribed substrate or inhibitor drugs of CYP2D6 ( P = 0.63), or whether they were a robust responder ( P = 0.47). Conclusions Urinary assays of CYP2D6 phenotype are technically feasible in older individuals with dementia who are taking multiple medications, and may be a useful clinical tool in this population. However, the study was unable to make inferences about an association between CYP2D6 phenotype and galantamine responsiveness.