Objectives: CYP2C9 gene polymorphic variants can decrease the effects of losartan, reducing active metabolite (E-3174) formation. Study aims to determine the influence of *2 (+430C>T; rs799853) and *3 (+1075A>C; rs1057910) CYP2C9 gene polymorphic variants on the hypotensive and uricosuric effect of losartan on patients with arterial hypertension. Methods: Eighty one patients with stage 1–2 arterial hypertension newly diagnosed with ABMP were enrolled in the study. Physicians started losartan treatment and then we measured urine concentration of E-3174/losartan to estimate CYP2C9 activity. After 3-month losartan treatment we compared effectiveness of the therapy with ABPM and plasma uric acid level between carriers of CYP2C9 *1/*1 and CYP2C9 gene polymorphic variants ( *2 and *3 ). Results: Carriage of CYP2C9*2 and CYP2C9*3 alleles reduced the hypotensive effect of losartan (p<0.001, OR=8.13 (95% CI, 2.75–23.97)). Analysis of the ABPM data revealed that blood pressure was significantly higher in patients with polymorphic genotypes. There was no significant difference in uric acid level in plasma and losartan and its metabolite concentration in urine between genotypes. Conclusions: Carriage of low function polymorphic variants of the CYP2C9 gene ( *2 and *3 ) reduced the hypotensive effect of losartan according to ABPM and don’t affect uric acid level in plasma and E-3174/losartan in urine.

This scientific review presents a current data on the effect of genetic polymorphism of CYP2C9 genes and genes encoding components of the renin-angiotensin-aldosterone system (RAAS) on the angiotensin II receptor blockers (ARBs) pharmacokinetics and pharmacodynamics. The data shows that genetic polymorphisms of these genes determine the large interindividual variability of the pharmacological response to ARBs. In this article, we carried out a comprehensive review of recent findings on interpatient variability in antihypertensive therapy response due to genetic factors and individualized treatment approach in ARBs therapy.

Background . Helicobacter pylori infection is a major risk factor for gastric cancer, and its eradication is considered a primary preventive measure. Proton pump inhibitors (PPIs) are a cornerstone of eradication therapy, but their efficacy is significantly influenced by genetic polymorphisms in the CYP2C19 enzyme, which is responsible for their metabolism. Objective. To summarize and present current research on the impact of CYP2C19 genetic polymorphism on the effectiveness of H. pylori eradication therapy. Materials and methods . A literature review was conducted using Russian and international databases (RSCI, PubMed, ResearchGate) with keywords including "CYP2C19 polymorphism," "proton pump inhibitor metabolism," and "Helicobacter pylori eradication." A total of 41 publications most relevant to the topic were analyzed. Results. The metabolism of first-generation PPIs (omeprazole, lansoprazole, pantoprazole) is highly dependent on CYP2C19 activity. Patients are classified into different metabolic phenotypes (ultrarapid – UM, rapid – RM, normal – NM, intermediate – IM, poor – PM) based on their CYP2C19 genotype. Evidence, primarily from Asian populations, indicates that NM and RM/UM phenotypes are associated with lower eradication rates due to accelerated PPI metabolism and reduced drug exposure, whereas IM and PM phenotypes show higher efficacy. The Russian population has a high frequency of the rapid metabolizer allele CYP2C19*17, suggesting potential suboptimal response to standard PPI doses. Rabeprazole and esomeprazole demonstrate less dependence on CYP2C19, leading to more consistent efficacy across different genotypes. Clinical guidelines (e.g., CPIC, DPWG) recommend genotype-guided PPI dosing to optimize therapy. Conclusion . CYP2C19 genetic polymorphism is a critical determinant of PPI pharmacokinetics and the effectiveness of H. pylori eradication. Pharmacogenetic testing for CYP2C19 can be a valuable tool for personalizing anti-Helicobacter therapy, particularly in populations with a high prevalence of rapid metabolizer alleles, by enabling the selection of the most appropriate PPI and its dose to overcome refractoriness and improve treatment outcomes.