Westergaard Niels, Søgaard Nielsen Regitze, Jørgensen Steffen, Vermehren Charlotte
Centre for Engineering and Science, Department of Biomedical Laboratory Science, University College Absalon, Parkvej 190, 4700 Naestved, Denmark.
Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.
J Pers Med. 2020 Jan 16;10(1):3. doi: 10.3390/jpm10010003.
The cytochrome P450 drug metabolizing enzymes CYP2D6 and CYP2C19 are the major targets for pharmacogenomics (PGx) testing and determining for drug response. Clinical dosing guidelines for specific drug-gene interactions (DGI) are publicly available through PharmGKB. The aim of this register study was to map the use of drugs in Denmark for drugs having actionable dosing guidelines (AG) i.e., dosing recommendations different from standard dosing for CYP2D6 or CYP2C19 DGI in terms of consumption.
The Danish Register of Medicinal Product Statistics was the source to retrieve consumption in Defined Daily Dose (DDD) i.e., the assumed average maintenance dose per day for a drug used for its main indication in adults and number of users (2017 data). Clinical dosing guidelines were available from the PharmGKB website.
Forty-nine drugs have guidelines corresponding to 14.5% of total sales in DDD. Twenty-eight drugs have AG corresponding to 375.2 million DDD. Pantoprazole, lansoprazole, omeprazole, clopidogrel, and metoprolol constituted fifty-eight percent of the consumption in DDD of drugs having AG. The consumption of antidepressant drugs, opioids, and antipsychotic drugs were 157.0 million DDD; with 441,850 users, 48.9 million DDD; with 427,765 users, and 23.7 million DDD; with 128,935 users, respectively. Age distributions of consumption of drugs and drug combinations, e.g., for sertraline redeemed either alone or in combination with metoprolol and tramadol, are presented.
This exploratory register study clearly showed that a large fraction of the Danish population, especially the elderly, are exposed to drugs or drug combinations for which there exist AG related to PGx of CYP2D6 or CYP2C19.
细胞色素P450药物代谢酶CYP2D6和CYP2C19是药物基因组学(PGx)检测及确定药物反应的主要靶点。特定药物-基因相互作用(DGI)的临床给药指南可通过药物基因组学知识数据库(PharmGKB)公开获取。本登记研究的目的是梳理丹麦具有可操作给药指南(AG)的药物使用情况,即就消耗量而言,针对CYP2D6或CYP2C19 DGI的给药建议不同于标准给药。
丹麦药品统计登记册是获取限定日剂量(DDD)消耗量的来源,即假定用于其主要适应证的成人药物每日平均维持剂量以及使用者数量(2017年数据)。临床给药指南可从PharmGKB网站获取。
49种药物有相应指南,占DDD总销售额的14.5%。28种药物有AG,相当于3.752亿DDD。泮托拉唑、兰索拉唑、奥美拉唑、氯吡格雷和美托洛尔占具有AG药物DDD消耗量的58%。抗抑郁药、阿片类药物和抗精神病药物的消耗量分别为1.570亿DDD(使用者441,850人)、4890万DDD(使用者427,765人)和2370万DDD(使用者128,935人)。呈现了药物及药物组合(如舍曲林单独使用或与美托洛尔和曲马多联合使用)消耗量的年龄分布情况。
这项探索性登记研究清楚地表明,丹麦很大一部分人口,尤其是老年人,接触到了与CYP2D6或CYP2C19的PGx相关的AG的药物或药物组合。