Cytochrome P-450 gene and drug interaction analysis in patients referred for pharmacogenetic testing.

Purpose: 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.

Conclusion: 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.