Pharmacogenetics of Drug–Drug Interaction and Drug–Drug–Gene Interaction: A Systematic Review on CYP2C9, CYP2C19 and CYP2D6

Abstract

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.

Keywords::

• CYP2C19
• CYP2C9
• CYP2D6
• drug–drug–gene interaction (DDGI)
• drug–drug interaction (DDI)
• drug-metabolizing enzyme

Acknowledgements

MA Bahar and D Setiawan obtained a DIKTI scholarship from the Ministry of Research, Technology and Higher Education of Indonesia. We thanked KI Sijtsma from Centrale Medische Bibliotheek, Universitair Medisch Centrum Groningen (UMCG), for her assistance in building the search strategy used in this review.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.