Clarke Jo-Anne, Cutler Murray, Gong Inna, Schwarz Ute I, Freeman David, Dasgupta Monidipa
Division of Geriatric Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada.
Am J Geriatr Pharmacother. 2011 Aug;9(4):224-33. doi: 10.1016/j.amjopharm.2011.07.003. Epub 2011 Jul 30.
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.
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.
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.
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).
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.
细胞色素P450（CYP）2D6酶参与许多老年人群使用的药物的代谢。其活性的变化可导致药物反应改变。然而，关于该酶系统活性的研究很少纳入老年人群。
本初步研究的目的是评估在患有痴呆症的老年人群中对CYP2D6进行体内表型分析的可行性，并确定加兰他敏治疗反应的部分变异性是否归因于CYP2D6表型。
参加老年门诊且接受加兰他敏治疗至少6个月的痴呆症患者被纳入本病例对照研究。在摄入30mg右美沙芬后，通过分析探针药物右美沙芬及其主要代谢产物右啡烷的尿浓度来确定CYP2D6表型。如果患者在治疗6个月后的认知测试（使用简易精神状态检查表或阿尔茨海默病评估量表 - 认知分量表评分）没有变化或有所改善，则被归类为对加兰他敏反应良好的患者。
43名患者（23名男性，20名女性；平均年龄78.4岁；98%为白人）接受了表型分析。同时开具的药物平均数量为5.7种，16名患者（37%）正在接受其他CYP2D6底物或抑制剂药物治疗。CYP2D6表型的分布与其他白人人群相似。表型代谢率与年龄、常规服用药物的数量、患者是否正在接受其他CYP2D6规定的底物或抑制剂药物（P = 0.63）或他们是否是反应良好的患者（P = 0.47）之间均无相关性。
对服用多种药物的老年痴呆症患者进行CYP2D6表型的尿液检测在技术上是可行的，并且可能是该人群中一种有用的临床工具。然而，该研究无法推断CYP2D6表型与加兰他敏反应性之间的关联。
