Effects of CYP2C19 Polymorphism on Metabolism and Effectiveness of Proton Pump Inhibitors: A Review of Clinical and Laboratory Studies

Abstract

Introduction: Establishing the reasons for the decrease in the effectiveness of anti-Helicobacter pylori therapy and proton pump inhibitors in the treatment of acid-dependent diseases is an urgent task due to high prevalence of these disorders undermining population health. Our objective was to conduct a literature review to assess the influence of the genetic polymorphism of cytochrome P-450 CYP2C19 on the eradication rate of Helicobacter pylori and the metabolism of proton pump inhibitors, to evaluate the effectiveness of their use, and to determine possible ways of overcoming refractoriness to these drugs in the clinic. Materials and methods: We analyzed published studies found in domestic (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases. Results: We revealed a genetic polymorphism CYP2C19 of cytochrome P-450, according to which different types of drug metabolism were identified: fast, intermediate, slow, and ultrafast. The relationship of this polymorphism with biotransformation of proton pump inhibitors was then analyzed. In Russia, the predominance of fast and intermediate metabolism in individuals of the Caucasian race decreases the efficacy of acid-suppressive therapy and the Helicobacter pylori eradication rate. Correction of the daily dose and frequency of drug administration are necessary to increase the antisecretory effect of proton pump inhibitors. Discussion: The dependence of proton pump inhibitor biotransformation on the CYP2C19 polymorphism determines the differences between patients with different types of metabolism in the effectiveness of these drugs, the success of anti-Helicobacter pylori treatment, and clinical outcomes. Pharmacogenetic testing is useful for predicting the response to proton pump inhibitors, the likelihood of developing adverse events, and the possibility of personalized prescriptions in patients with acid-related diseases. Conclusion: Genetic testing of cytochrome CYP2C19 helps optimize the use of proton pump inhibitors, overcome refractoriness, and improve the quality of treatment of acid-dependent diseases and the overall Helicobacter pylori eradication rate.