A priority in the development of modern healthcare is patient-centered medicine, the main tool of which is the ability to predict the individual response to certain interventions, including the use of medications. This is made possible through the use of knowledge-intensive technologies that provide the detection of certain biomarkers, making it possible to obtain individual information about the patient, in order to personalize the choice and dosing regimen of drugs. The most promising for clinical practice are pharmacogenetic/pharmacogenomic, pharmacoepigenomic and pharmacometabolomic biomarkers.

Anxiety and depression are very common during pregnancy. Post-partum period may frequently be complicated by more pro found depression due to hormonal changes, which may lead to fatal consequences for both — the mother and the child. The most commonly prescribed group of drugs for ambulatory patient care is the group of selective serotonine reuptake inhibitors (SSRIs). Absence of clinical trials where pregnant or breast-feeding women were among the participants has led to the situation when we can rule out effectiveness and safety of this drug class for pregnant and breastfeeding women based only on real-life studies. Current know ledge let us conclude that all individual group representatives have comparable efficacy and safety profile. The choice of a single agent to use may be difficult. In our paper we analyzed genetic and non-genetic factors, that may be important for individual pharmacokinetics of various SSRIs in order to reveal the most relevant for each group representative, and to determine those drugs with the most stable pharmacokinetic parameters in pregnancy. We also tried to define the drugs that may theoretically be more clinically reliable and safe for the fetus and the newborn. We considered such factors as expected changes in drug concentration during various periods in pregnancy, probable impact of pre-existing pharmacogenetic factors of individual drug exposure, potential for drug-drug interactions, and current knowledge about the extent of drug distribution in the blood of the newborns during breastfeeding

This article discusses issues related to the role of biotransformation or metabolism of antipsychotics (APs) in the liver. There are three phases of APs metabolism. Cytochrome P450 monooxygenase, an oxidase with mixed functions, plays a key role in the biotransformation of most APs, participating in the first phase of metabolism. The functional activity of cytochrome P450 enzymes depends on the carriage of single nucleotide variants (SNVs) of the genes encoding these enzymes, as well as on drug-drug interactions. The functional activity of cytochrome P450 enzymes may affect the efficacy and safety of the use of APs. It is important for a practicing psychiatrist to know the pathways of APs oxidation to prevent adverse drug reactions (ADRs) and unwanted drug-drug interactions, which will subsequently increase the efficacy and safety of AP therapy

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed medications; however, their use may be associated with the development of numerous adverse reactions. Purpose of work: to analyze the data of studies, in which the influence of pharmacogenetic features of patients on the safety of NSAID therapy was studied. The results of numerous studies show that the safety of NSAIDs may be associated with the CYP2C9, CYP2C8, PTGS1 and PTGS2 polymorphisms. The allele frequency of these genes varies in different ethnic groups. Thus, the development of a personalized approach based on genetic, clinical and demographic, and ethnic factors of patients will improve the safety of NSAID therapy

Anticonvulsants or antiepileptic drugs (AEDs) are widely used for various neurological and psychiatric diseases and are often prescribed for a long period. In this regard, the issue of their safety profile is acute, including risk assessment for the development of life-threatening conditions and adverse drug reactions (ADRs). From the point of view of personalized medicine, it is important to develop an interdisciplinary approach to the development of a new strategy for a personalized approach to predicting AED-induced prolongation of the QT interval as one of the most unfavorable prognostic cardiac ADRs (including sudden death syndrome — SDS). We searched the databases of full-text publications for the period from 2012 to 2022 for keywords and their combinations. We have discovered and systematized monogenic and multifactorial forms of long QT syndrome (LQTS) and candidate genes that slow down AEDs metabolism in the liver. Identification of risk alleles of single nucleotide variants (SNV) of candidate genes predisposing to the development of AED-induced LQTS and SDS will allow adjusting the choice and dosage of these drugs and preventing the development of the ADR, which will improve the quality of life and help prevent SDS in patients with mental and neurological disorders

Relevance. The problem of antiplatelet therapy resistance is not fully solved, whereas its manifestations in the form of stent thrombosis cause a negative contribution in treatment and can lead to significant economic damage to the healthcare system. Pharmacogenetic testing as a personalization tool can potentially reduce the cost of treatment, which requires pharmacoeconomic research of pharmacogenetic methods. The aim of this study was a pharmacoeconomic evaluation of the pharmacogenetic testing implementation before the antiplatelet therapy in patients with acute coronary syndrome after percutaneous coronary intervention. Methods. In our study, a decision tree model was built with a time horizon of 1 year and a cost-effectiveness analysis was performed for six compared treatment strategies in patients with acute coronary syndrome after stent implantation with and without genotyping for the drugs clopidogrel, ticagrelor and prasugrel. Results. A treatment strategy with pharmacogenetic testing and the choosing of prasugrel for slow and intermediate metabolizers was the most preferred with CER 35 577.40 rubles per 1 unit of effectiveness. The most expensive strategy was the “blind” use of ticagrelor for all patients. Conclusion. Based on the modeling results, it can be concluded that the implementation of pharmacogenetic testing before prescribing antiplatelet drugs in patients with acute coronary syndrome undergoing stenting can potentially reduce the incidence of adverse events such as stent thrombosis and reduce the overall cost of treatment.

Relevance. Endocrine therapy is the standard treatment for women with ER-positive breast cancer. The clinical response to Tamoxifen is variable. Approximately 30 % of patients with breast cancer will have a recurrence of the disease within 15 years after treatment, despite ongoing endocrine therapy. This article presents the results of a prospective pharmacogenetic cohort study. The study was conducted in 2018–2019. Aim. To analyze adverse drug reactions to Tamoxifen in the adjuvant regimen in breast cancer patients in relation to the carriage of genetic polymorphisms of genes encoding cytochrome P450 enzymes and drug transporter proteins and to build predictive models based on them. A comparative analysis of the relationship between genetic and non-genetic determinants with adverse events on tamoxifen therapy allowed us to build predictive models of their development. Materials and Methods. The study involved 120 women with pre- and postmenopausal breast cancer who underwent genetic testing for CYP and Pg enzyme gene polymorphisms. Entry criteria: a histologically confirmed diagnosis of breast cancer, taking Tamoxifen at the recommended doses, establishing a diagnosis not earlier than 2007, and obtaining informed voluntary consent to participate in the study. Allelic variants were determined using real-time polymerase chain reaction in the Research Institute for Molecular and Personalized Medicine of the Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian Federation. Results. An associative analysis showed their association with the development of adverse drug reactions (ADR) to Tamoxifen, indicating the clinical significance of different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9 and ABCB1. The complex associative analysis performed using mathematical modeling made it possible to build predictive risk models for the development of such ADR, such as hot flashes, dyspepsia, bone pain, and asthenia. The resulting regression models were statistically significant (p < 0,001) and demonstrated high diagnostic efficiency. This allows them to be implemented in clinical practice. Conclusion. Thus, models that include both genetic and non-genetic determinants of response may further improve the prediction of individual response to tamoxifen

Objective. To demonstrate on a clinical example the importance of conducting pharmacogenetic testing in patients with ischemic stroke receiving clopidogrel in order to identify the polymorphic carriage of CYP2C19*17 (C806T, rs12248560). Materials and methods. A clinical and laboratory examination of 121 patients with ischemic stroke was carried out, the CYP2C19*17 polymorphism (C806T, rs12248560) associated with an increase in the effectiveness of clopidogrel, low residual platelet reactivity, and an increased risk of bleeding was determined. Carriage of polymorphic markers was determined by real-time polymerase chain reaction. Results and conclusion. In two patients (1.7 %), carriers of polymorphic markers CYP2C19*17, hemorrhagic cerebrovascular complications were detected on the background of clopidogrel. Gastrointestinal bleeding, as well as other complications of antiplatelet therapy, are not registered in practice