title: Cytochrome P-450 gene and drug interaction analysis in patients referred for pharmacogenetic testing.
abstract: OBJECTIVE
  The results of a study of variant cytochrome P-450 (CYP) alleles and associated risks of drug-drug interactions (DDIs) and altered drug metabolism are reported.
  
  
  METHODS
  The records of a pharmacogenetic testing laboratory were retrospectively analyzed to identify patients tested for polymorphisms of genes coding for five CYP isozymes important in drug metabolism (CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5) over a 16-month period. Based on the results of phenotyping, the patients were categorized by expected CYP isozyme activity (e.g., normal or poor metabolizer, expresser or nonexpresser). Using proprietary Web-based software, researchers analyzed phenotyping data and medication lists submitted by patients to determine the potential for DDIs, drug-gene interactions (DGIs), and drug-drug-gene interactions (DDGIs).
  
  
  RESULTS
  In the mixed-race study population of more than 22,000 male and female patients (age range, 1-108 years; mean, 60 years), phenotypes associated with alterations of CYP metabolic pathways were common. Among patients in whom phenotypes for all five isozymes of interest were determined (n = 14,578), about 93% were not categorized as normal metabolizers of all five proteins. In many cases, potential interaction threats were rated by clinicians as severe enough to warrant implementation or consideration of a medication regimen change or dose adjustment. Analysis of patient-provided medication lists indicated frequent use of medications posing DDI, DGI, or DDGI risks.
  
  
  CONCLUSIONS
  In a mixed-race population of over 20,000 U.S. patients, CYP gene polymorphisms associated with DDIs and other interaction threats were prevalent, and most individuals were not categorized as normal metabolizers of all five CYP isozymes of interest.
authors.affiliation: Genelex Corporation, Seattle, WA (bhocum@genelex.com).
authors.forename: Brian Thomas
authors.initials: BT
authors.lastname: Hocum
authors.affiliation: Department of Pharmaco-therapy, College of Pharmacy, Washington State University, Spokane, WA.
authors.forename: John Raymond
authors.initials: JR
authors.lastname: White
authors.affiliation: Genelex Corporation, Seattle, WA.
authors.forename: Jarrod W
authors.initials: JW
authors.lastname: Heck
authors.affiliation: Genelex Corporation, Seattle, WA.
authors.forename: Ranjit K
authors.initials: RK
authors.lastname: Thirumaran
authors.affiliation: Genelex Corporation, Seattle, WA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Moyer
authors.affiliation: Genelex Corporation, Seattle, WA.
authors.forename: Richard
authors.initials: R
authors.lastname: Newman
authors.affiliation: Genelex Corporation, Seattle, WA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Ashcraft
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology*; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012017:Referral and Consultation; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System