g-Nomic: a new pharmacogenetics interpretation software

Abstract

We present g-Nomic, a pharmacogenetics interpretation software that analyzes globally a prescribed medication taking into account the personal background genetics, drug-drug interactions, lifestyle, nutritional supplements, inhibitors, inducers, and other risks to analyze primary or secondary metabolism pathways. G-Nomic provides a set of recommendations describing the suitability of a given combination of drugs for each patient according to their genes and polymedication. G-Nomic is updated monthly including data from the new drugs to be included, their known interactions, and the relevant pharmacokinetic biomarkers. For the interactions, the list is curated manually, only keeping those with clinical relevance. For each drug, their FDA and EMA drug labels are accessed, to check for relevant enzymes and transport proteins that influence its pharmacokinetics, and for their ability to induce or inhibit other enzymes, particularly the CYP-450 system. When this information is not available, a PubMed search is made to look for these characteristics. In addition, a distinction is made between drugs and prodrugs. A query on the g-Nomic software begins with entering the medication by either their common or commercial name. Non-pharmacological substances can be also added or selected under "lifestyle habits". The lifestyle list is dynamic, showing only the substances known to interact with the drugs that are currently selected, and includes herb compounds, such as St. John's wort, as well as proper lifestyle substances such as grapefruit or cigarette smoking. The software provides a list of the genes classified as primary biomarkers as candidates for genetic testing, and a list of the interactions that have been detected. If genetic information is available then, or is made available at a later point, these results can also be entered and the software returns pharmacogenetics recommendations regarding specific genotypes. g-Nomic takes all the above-mentioned parameters in an easy and user-friendly tool making prescription safer.

Keywords: SNP; drug-drug interaction; drug-herb; drug-lifestyle; pharmacogenetics; software.

Figure 1

Patient reality when taking a drug. It is shown the different elements analyzed and taken into account by the interpretation software g-Nomic: Primary (PP) or secondary (SP) pathways, personal background genetics – Extensive (EM), Intermediate (IM), Ultra (UM), and Poor (PM) Metabolizers, drug–drug interactions, lifestyle, nutritional supplements inhibitors and inducers, and other risks.

Figure 2

g-Nomic pharmacogenetics report for aripiprazole of a patient showing a PM CYP2D6 phenotype.

Figure 3

g-Nomic pharmacogenetics report for a CYP2D6 PM individual prescribed with tamoxifen.

Figure 4

Drug interaction between simvastatin and ticagrelor: The two drugs are metabolized by CYP3A4.

Figure 5

Interpretion of g-Nomic in the case of drug–lifestyle interaction: Tamoxifen plus calcium.

Figure 6

g-Nomic report in the case of the prodrug inhibition caused by paroxetine on the formation of endoxifen from tamoxifen.

Figure 7

g-Nomic report in case of the drug induction of several cytochrome P-450 enzymes produced by Rifampin which may low plasma levels of drugs such as Paroxetine.

Figure 8

g-Nomic report showing risks associated with specific medications.