Deb Subrata, Hopefl Robert, Reeves Anthony Allen, Cvetkovic Dena
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA.
Medicines (Basel). 2024 Feb 20;11(3):6. doi: 10.3390/medicines11030006.
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.
药物基因组学（PGx）有助于向针对患者的药物治疗方案转变，从而提高疗效并降低毒性。本研究的目的是评估美国食品药品监督管理局（FDA）的PGx标签和临床药物遗传学实施联盟（CPIC）数据库中药物吸收、分布、代谢和排泄（ADME）相关基因的PGx分类的重叠情况。在CPIC数据库中识别出FDA批准的药物和ADME基因的PGx标签。通过药物与ADME（药代动力学）相关基因的关联、PGx FDA标签类别和CPIC证据水平对药物进行筛选。FDA的PGx标签分为可操作、信息性、推荐检测或要求检测，CPIC证据水平分为A、B、C或D。在CPIC数据库中总共442个ADME和非ADME基因-药物对中，分别有273、55和48对因缺乏FDA标签、CPIC证据水平混合的临时分类以及非ADME基因-药物对而被排除。66个ADME基因-药物对被分为以下几类：10个（15%）信息性、49个（74%）可操作、6个（9%）推荐检测和1个（2%）要求检测。CYP2D6是FDA PGx标签中最常见的基因。在具有FDA和CPIC PGx分类的ADME基因-药物对中，大多数药物用于治疗抑郁症、癌症和疼痛。具有FDA PGx标签的ADME基因-药物对与CPIC分类有相当大的重叠；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FDA PGx标签中最常见的ADME基因。卫生专业人员可以通过分析和协调FDA标签与CPIC数据库，通过药物遗传学干预来影响治疗效果。
