CYP2C19 polymorphism in relation to the pharmacotherapy optimization of commonly used drugs

Pharmazie. 2018 Nov 1;73(11):619-624. doi: 10.1691/ph.2018.8689.

Abstract

Purpose: The CYP2C19 isoenzyme plays an important role in the efficacy and safe use of many drugs. The aim of this review is to demonstrate how CYP2C19 mutations influence everyday patient treatment, leading to adverse drug reactions or therapy failure in many common diseases. Methods: A PubMed literature search was performed on clinical publications evaluating the impact of CYP2C19 on pharmacotherapy outcome. Main fields of medicine with strong outcome dependency on the CYP2C19 genotype were selected. We also focused on clinical recommendations for the use of drugs referring to CYP2C19 polymorphism. Results: The fields of medicine where clinical outcome particularly depends on CYP2C19 polymorphism are gastroenterology, cardiology, psychiatry, mycology and oncology. CYP2C19 is involved in proton pump inhibitors metabolism, thus it can influence reflux therapy, ulcer prevention and Helicobacter pylori eradication treatment. The CYP2C19 enzyme plays also a vital role in the two bioactivation steps of clopidogrel leading to lower (CYP2C19*17 carriers) or higher (CYP2C19*2 carriers) risk of major adverse cardiovascular events. It affects the antidepressant treatment and methadone replacement therapy as well as voriconazole prophylaxis. The presence of a *2 allele is associated with longer relapse-free time or better survival, and the *17 allele with more favorable outcomes in breast cancer patients treated with tamoxifen. Conclusions: Knowledge of the CYP2C19 polymorphism could positively affect individual treatment and lead to better patient outcomes in many cases. The introduction of pharmacogenetic testing into medical practice would be a good way to minimize negative outcomes of therapy, and to reduce unnecessary medical costs.

Publication types

  • Review

MeSH terms

  • Alleles
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Genotype
  • Humans
  • Mutation
  • Pharmaceutical Preparations / metabolism*
  • Pharmacogenetics*
  • Polymorphism, Genetic

Substances

  • Pharmaceutical Preparations
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19