CYP2C19 drug-drug and drug-gene interactions in ED patients

Am J Emerg Med. 2016 Feb;34(2):245-9. doi: 10.1016/j.ajem.2015.10.055. Epub 2015 Nov 9.

Abstract

Background: CYP450 polymorphisms result in variable rates of drug metabolism. CYP drug-drug interactions can contribute to altered drug effectiveness and safety.

Study objectives: The primary objective was to determine the percentage of emergency department (ED) patients with cytochrome 2C19 (CYP2C19) drug-drug interactions. The secondary objective was to determine the prevalence of CYP2C19 polymorphisms in a US ED population.

Methods: We conducted a prospective observational study in an urban academic ED with 72,000 annual visits. Drug ingestion histories for the 48 hours preceding ED visit were obtained; each drug was coded as CYP2C19 substrate, inhibitor, inducer, or not CYP2C19 dependent. Ten percent of patients were randomized to undergo CYP2C19 genotyping using the Roche Amplichip.

Results: A total of 502 patients were included; 61% were female, 65% were white, and median age was 39 years (interquartile range, 22-53). One hundred thirty-one (26.1%) patients had taken at least 1 CYP2C19-dependent home drug. Eighteen (13.7%) patients who were already taking a CYP2C19-dependent drug were given or prescribed a CYP2C19-dependent drug while in the ED. Among the 53 patients genotyped, 52 (98%) were extensive metabolizers and 1 was a poor metabolizer.

Conclusions: In a population of ED patients, more than a quarter had taken a CYP2C19-dependent drug in the preceding 48 hours, but few were given or prescribed another CYP2C19-dependent drug in the ED. On genotyping analysis, CYP2C19 polymorphisms were uncommon in our cohort. We conclude that changing prescribing practice due to CYP2C19 drug-drug interaction or genotype is unlikely to be useful in most US ED populations.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cytochrome P-450 CYP2C19 / genetics*
  • Drug Interactions / genetics*
  • Emergency Service, Hospital
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics / methods*
  • Polymorphism, Genetic*
  • Prevalence
  • Prospective Studies
  • United States / epidemiology

Substances

  • Cytochrome P-450 CYP2C19