Frequencies of Combined Dysfunction of Cytochromes P450 2C9, 2C19, and 2D6 in an Italian Cohort: Suggestions for a More Appropriate Medication Prescribing Process

Int J Mol Sci. 2023 Aug 11;24(16):12696. doi: 10.3390/ijms241612696.

Abstract

Improper drug prescription is a main cause of both drug-related harms (inefficacy and toxicity) and ineffective spending and waste of the healthcare system's resources. Nowadays, strategies to support an improved, informed prescription process may benefit from the adequate use of pharmacogenomic testing. Using next-generation sequencing, we analyzed the genomic profile for three major cytochromes P450 (CYP2C9, CYP2C19, CYP2D6) and studied the frequencies of dysfunctional isozymes (e.g., poor, intermediate, or rapid/ultra-rapid metabolizers) in a cohort of 298 Italian subjects. We found just 14.8% of subjects with a fully normal set of cytochromes, whereas 26.5% of subjects had combined cytochrome dysfunction (more than one isozyme involved). As improper drug prescription is more frequent, and more burdening, in polytreated patients, since drug-drug interactions also cause patient harm, we discuss the potential benefits of a more comprehensive PGX testing approach to support informed drug selection in such patients.

Keywords: CYP2C19; CYP2C9; CYP2D6; adverse drug reactions; co-prescription; cytochrome P450; drug–drug interactions; pharmacogenomics; polypharmacy.

MeSH terms

  • Cytochrome P-450 CYP2C9 / genetics
  • Cytochrome P-450 CYP2D6*
  • Drug Prescriptions*
  • Genetic Profile
  • High-Throughput Nucleotide Sequencing
  • Humans

Substances

  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP2D6

Grants and funding

This research received no external funding.