How Common are Drug and Gene Interactions? Prevalence in a Sample of 1143 Patients with CYP2C9, CYP2C19 and CYP2D6 Genotyping

Abstract

Aim: Drug–drug interactions (DDIs) are a widely recognized major cause of adverse drug reactions, but two other newly described important types of interactions also exist: drug–gene interactions (DGIs) and drug–drug–gene interactions (DDGIs). A drug–gene interaction occurs when a patient‘s genetic CYP450 type (e.g., CYP2D6 poor metabolizer) affects that patient‘s ability to clear a drug. A drug–drug–gene interaction occurs when the patient‘s CYP450 genotype and another drug in the patient‘s regimen (e.g., a CYP2D6 inhibitor) affect that individual‘s ability to clear a drug. Their prevalence has not been previously described. This pilot study investigates the frequency of DDIs, DGIs and DDGIs in a sample of CYP450 tested individuals. Materials & methods: The investigators conducted a retrospective analysis of 1143 individuals with known CYP2D6, CYP2C19 and CYP2C9 genotypes. Using the individuals‘ medication lists and YouScript^®, a software tool to analyze cumulative DDIs and DGIs, the prevalence of DDI, DGI and DDGIs was analyzed. Results: A total of 1053 potential major or substantial interactions were identified in 501 individuals. DDIs accounted for 66.1% of the total interactions. The remaining 33.9% of interactions were DGIs (14.7%) and DDGIs (19.2%). When compared with DDIs alone, DGIs and DDGIs increased the total number of potentially clinically significant interactions by 51.3%. Conclusion: In the future, identifying DGIs and DDGIs may lead to a more comprehensive method of identifying individuals who are at risk for adverse drug reactions.

Original submitted 3 May 2013; Revision submitted 6 January 2014

KEYWORDS::

• CYP2C19
• CYP2C9
• CYP2D6
• CYP450
• cytochrome
• drug interactions
• drug–drug
• drug–gene
• personalized medicine
• pharmacogenomics
• polymorphism

Financial & competing interests disclosure

This study was funded by Genelex Corporation of Seattle, WA, USA. J Oesterheld has an equity interest in Genelex and holds the patent for the YouScript^® software. In addition, P Verbeurgt, T Mamiya and J Oesterheld are currently employed by Genelex Corporation. The authors would like to thank the following people for their contributions: J Gaines and J Marquis for their assistance with the preparation of the manuscript; R Pany and A Raju for their assistance in data extraction; and E Peletskaya and T Aulinskas for their contribution to interpretation of genetic laboratory results. In addition the authors would like to thank K Lambert, K Ashcraft, H Coleman and B Patterson for their editorial comments and assistance. All contributors are either employees and/or stockholders of Genelex Corporation. The authors have no other 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 apart from those disclosed.

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

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was funded by Genelex Corporation of Seattle, WA, USA. J Oesterheld has an equity interest in Genelex and holds the patent for the YouScript^® software. In addition, P Verbeurgt, T Mamiya and J Oesterheld are currently employed by Genelex Corporation. The authors would like to thank the following people for their contributions: J Gaines and J Marquis for their assistance with the preparation of the manuscript; R Pany and A Raju for their assistance in data extraction; and E Peletskaya and T Aulinskas for their contribution to interpretation of genetic laboratory results. In addition the authors would like to thank K Lambert, K Ashcraft, H Coleman and B Patterson for their editorial comments and assistance. All contributors are either employees and/or stockholders of Genelex Corporation. The authors have no other 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 apart from those disclosed. No writing assistance was utilized in the production of this manuscript.