title: How common are drug and gene interactions? Prevalence in a sample of 1143 patients with CYP2C9, CYP2C19 and CYP2D6 genotyping.
abstract: OBJECTIVE
  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.
  
  
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genelex Corporation, 3101 Western Avenue #100, Seattle, WA 98121, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Verbeurgt
authors.forename: Tyler
authors.initials: T
authors.lastname: Mamiya
authors.forename: Jessica
authors.initials: J
authors.lastname: Oesterheld
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010595:Pharmacists; D015995:Prevalence; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D065729:Cytochrome P-450 CYP2C9; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6