Reeves Anthony Allen, Hopefl Robert, Deb Subrata
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, USA.
Drug Metab Pers Ther. 2022 Oct 19;38(1):65-78. doi: 10.1515/dmpt-2022-0123. eCollection 2023 Mar 1.
Clinical Pharmacogenetics Implementation Consortium (CPIC) is a platform that advances the pharmacogenomics (PGx) practice by developing evidence-based guidelines. The purpose of this study was to analyze the CPIC database for ADME related genes and their corresponding drugs, and evidence level for drug-gene pairs; and to determine the presence of these drug-gene pairs in the highest mortality diseases in the United States.
CPIC database was evaluated for drug-gene pairs related to absorption, distribution, metabolism, and excretion (ADME) properties. National Vital Statistics from Centers for Disease Control and Prevention was used to identify the diseases with the highest mortality. CPIC levels are assigned to different drug-gene pairs based on varying levels of evidence as either A, B, C, or D. All drug-gene pairs assigned with A/B, B/C, or C/D mixed levels were excluded from this study. A stepwise exclusion process was followed to determine the prevalence of various ADME drug-gene pairs among phase I/II enzymes or transporters and stratify the drug-gene pairs relevant to different disease conditions most commonly responsible for death in the United States.
From a total of 442 drug-gene pairs in the CPIC database, after exclusion of 86 drug-gene pairs with levels A/B, B/C, or C/D, and 211 non-ADME related genes, 145 ADME related drug-gene pairs resulted. From the 145 ADME related drug-genes pairs, the following were the distribution of levels: Level A: 43 (30%), Level B: 22 (15%), Level C: 59 (41%), Level D: 21 (14%). The most prevalent ADME gene with CPIC level A classification was cytochrome P450 2C9 () (26%) and overall, the most prevalent ADME gene in the CPIC database was (30%). The most prevalent diseases related to the CPIC evidence related drugs were cancer and depression.
We found that there is an abundance of ADME related genes in the CPIC database, including in the high mortality disease states of cancer and depression. There is a differential level of pharmacogenomic evidence in drug-gene pairs enlisted in CPIC where levels A and D having the greatest number of drug-gene pairs. was the most common ADME gene with CPIC evidence for drug-gene pairs. Pharmacogenomic applications of CPIC evidence can be leveraged to individualize patient therapy and lower adverse effect events.
临床药物基因组学实施联盟（CPIC）是一个通过制定循证指南来推进药物基因组学（PGx）实践的平台。本研究的目的是分析CPIC数据库中与药物吸收、分布、代谢和排泄（ADME）相关的基因及其相应药物，以及药物-基因对的证据水平；并确定这些药物-基因对在美国死亡率最高的疾病中的存在情况。
对CPIC数据库中与吸收、分布、代谢和排泄（ADME）特性相关的药物-基因对进行评估。使用美国疾病控制与预防中心的国家生命统计数据来确定死亡率最高的疾病。根据不同的证据水平，CPIC将不同的药物-基因对分为A、B、C或D级。本研究排除了所有被指定为A/B、B/C或C/D混合级别的药物-基因对。采用逐步排除法来确定I/II期酶或转运体中各种ADME药物-基因对的流行情况，并对与美国最常见的导致死亡的不同疾病状况相关的药物-基因对进行分层。
在CPIC数据库中的总共442个药物-基因对中，排除86个A/B、B/C或C/D级别的药物-基因对以及211个与ADME无关的基因后，得到了145个与ADME相关的药物-基因对。在这145个与ADME相关的药物-基因对中，证据水平分布如下：A级：43个（30%），B级：22个（15%），C级：59个（41%），D级：21个（14%）。CPIC证据水平为A级的最常见ADME基因是细胞色素P450 2C9（）（26%），总体而言，CPIC数据库中最常见的ADME基因是（30%）。与CPIC证据相关药物最相关的疾病是癌症和抑郁症。
我们发现CPIC数据库中有大量与ADME相关的基因，包括在癌症和抑郁症等高死亡率疾病状态中。CPIC中登记的药物-基因对的药物基因组学证据水平存在差异，其中A级和D级的药物-基因对数量最多。是CPIC中有药物-基因对证据的最常见ADME基因。可以利用CPIC证据的药物基因组学应用来实现患者治疗个体化并降低不良反应事件。
