PDF(Pubmed)
Abstract：
Pharmacogenomics (PGx) can facilitate the transition to patient-specific drug regimens and thus improve their efficacy and reduce toxicity. The aim of this study was to evaluate the overlap of PGx classification for drug absorption, distribution, metabolism, and elimination (ADME)-related genes in the U.S. Food and Drug Administration (FDA) PGx labeling and in the Clinical Pharmacogenetics Implementation Consortium (CPIC) database. FDA-approved drugs and PGx labeling for ADME genes were identified in the CPIC database. Drugs were filtered by their association with ADME (pharmacokinetics)-related genes, PGx FDA labeling class, and CPIC evidence level. FDA PGx labeling was classified as either actionable, informative, testing recommended, or testing required, and varying CPIC evidence levels as either A, B, C, or D. From a total of 442 ADME and non-ADME gene-drug pairs in the CPIC database, 273, 55, and 48 pairs were excluded for lack of FDA labeling, mixed CPIC evidence level provisional classification, and non-ADME gene-drug pairs, respectively. The 66 ADME gene-drug pairs were classified into the following categories: 10 (15%) informative, 49 (74%) actionable, 6 (9%) testing recommended, and 1 (2%) testing required. CYP2D6 was the most prevalent gene among the FDA PGx labeling. From the ADME gene-drug pairs with both FDA and CPIC PGx classification, the majority of the drugs were for depression, cancer, and pain medications. The ADME gene-drug pairs with FDA PGx labeling considerably overlap with CPIC classification; however, a large number of ADME gene-drug pairs have only CPIC evidence levels but not FDA classification. PGx actionable labeling was the most common classification, with CYP2D6 as the most prevalent ADME gene in the FDA PGx labeling. Health professionals can impact therapeutic outcomes via pharmacogenetic interventions by analyzing and reconciling the FDA labels and CPIC database.
摘要：
药物基因组学（PGx）可以促进向患者特异性药物方案的过渡，从而提高其疗效并降低毒性。这项研究的目的是评估PGx分类对药物吸收的重叠，分布，新陈代谢，美国食品和药物管理局（FDA）PGx标签和临床药物遗传学实施联盟（CPIC）数据库中与消除（ADME）相关的基因。在CPIC数据库中鉴定了FDA批准的药物和ADME基因的PGx标记。药物通过与ADME（药代动力学）相关基因的关联进行过滤，PGxFDA标签类，和CPIC证据水平。FDAPGx标签被归类为可采取行动，翔实，推荐测试,或需要测试，以及不同的CPIC证据水平，B,C,或D.从CPIC数据库中总共442对ADME和非ADME基因药物对中，273、55和48对因缺乏FDA标签而被排除在外，CPIC混合证据级别临时分类，和非ADME基因药物对，分别。66个ADME基因-药物对分为以下几类：10个（15%）信息，49（74%）可采取行动，6（9％）的测试建议，和1（2％）测试要求。CYP2D6是FDAPGx标记中最普遍的基因。从具有FDA和CPICPGx分类的ADME基因-药物对中，大多数药物是用于抑郁症的，癌症,和止痛药。带有FDAPGx标记的ADME基因-药物对与CPIC分类相当重叠；然而，大量的ADME基因-药物对只有CPIC证据水平,而没有FDA分类.PGx可操作标签是最常见的分类，CYP2D6是FDAPGx标记中最普遍的ADME基因。卫生专业人员可以通过分析和协调FDA标签和CPIC数据库，通过药物遗传学干预来影响治疗结果。
