Bahar Muh Akbar, Setiawan Didik, Hak Eelko, Wilffert Bob
Department of PharmacoTherapy, Epidemiology & Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia.
Pharmacogenomics. 2017 May;18(7):701-739. doi: 10.2217/pgs-2017-0194. Epub 2017 May 8.
Currently, most guidelines on drug-drug interaction (DDI) neither consider the potential effect of genetic polymorphism in the strength of the interaction nor do they account for the complex interaction caused by the combination of DDI and drug-gene interaction (DGI) where there are multiple biotransformation pathways, which is referred to as drug-drug-gene interaction (DDGI). In this systematic review, we report the impact of pharmacogenetics on DDI and DDGI in which three major drug-metabolizing enzymes - CYP2C9, CYP2C19 and CYP2D6 - are central. We observed that several DDI and DDGI are highly gene-dependent, leading to a different magnitude of interaction. Precision drug therapy should take pharmacogenetics into account when drug interactions in clinical practice are expected.
目前，大多数关于药物相互作用（DDI）的指南既未考虑基因多态性对相互作用强度的潜在影响，也未考虑由DDI与药物-基因相互作用（DGI）组合所导致的复杂相互作用，其中存在多种生物转化途径，这被称为药物-药物-基因相互作用（DDGI）。在本系统评价中，我们报告了药物遗传学对DDI和DDGI的影响，其中三种主要的药物代谢酶——CYP2C9、CYP2C19和CYP2D6——起着核心作用。我们观察到，几种DDI和DDGI高度依赖基因，导致相互作用的程度不同。在临床实践中预期会发生药物相互作用时，精准药物治疗应考虑药物遗传学。
