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

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disor ders; gastrointestinal disorders, neurological disorders, and allergic reactions; and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia; neutropenia is also characteristic of a number of interleukin inhibitors. Haemo static adverse reactions to anticoagulants depend on the patient’s dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.

Introduction. An outbreak of novel COVID-19 infection has become a real challenge for the entire human society, and first of all for the healthcare services. The development of new drugs is a complex and lengthy process. At the beginning of the pandemic, it forced an intensive study of well-known drugs for the therapy. Remdesivir was first investigated as a potential treatment for Ebola virus. After beginning of the COVID-19 pandemic, in vitro evaluations demonstrated its activity against SARS-CoV-2. Subsequent clinical studies showed the efficacy of remdesivir in shortening the time to recovery.Aim. To evaluate the effect of the carriage of polymorphic alleles of the CES1 gene (A > C, rs2244613) on the safety profile of remdesivir therapy.Materials and methods. A total of 154 patients hospitalized with coronavirus infection were included in the study. All patients received remdesivir as etiotropic therapy in the standard regimen: 200 mg on the first day followed by 100 mg daily for 5-10 days. In the course of observations, clinical and laboratory signs of adverse events were reported. Venous blood samples were collected from each patient for pharmacogenetic studies. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: вata were analysed by using IBM SPSS Statistics, Version 23.0.Results. There were no significant associations of carriage of various CES1 variants with the frequency of adverse reactions (bradycardia, nausea, vomiting) and laboratory markers of adverse events (ALT, AST, creatinine levels).Conclusion. In our study, no association was found between the carriage of CES1 gene polymorphisms and the safety parameters of remdesivir in hospitalized patients with COVID-19. Further research into the possibilities of personalizing COVID-19 therapy through pharmacogenetic testing is needed.

Цель исследования -оценить ассоциации полиморфных вариантов CYP3A5*3 6986 A > G rs776746 и CYP3A4*22 rs35599367 С > T с параметрами безопасности терапии ремдесивиром у пациентов с COVID-19. Материал и методы. В исследование было включено 156 пациентов, госпитализированных в ГКБ№15 ДЗМ с диагнозом COVID-19, получавших ремдесивир в качестве противовирусного препарата. Частота побочных реакций (брадикардии, диспепсические расстройства), а также различные лабораторные параметры (уровни АЛТ, АСТ, креатинина, ферритина, интерлейкина-6 и д-димера) сравнивались между носителями «дикого» и полиморфных вариантов изучаемых генов. Результаты. У носителей полиморфных вариантов CYP3A5*3 (GA+AA) уровень АЛТ после терапии ремдесивиром был выше, чем у носителей дикого варианта (GG). При сравнении уровня интерлейкина-6 после терапии ремдесивиром носители полиморфного варианта CYP3A4*22 (CT) гена имели достоверно больший показатель этого цитокина. Заключение. Выявили ассоциацию носительства полиморфных вариантов CYP3A5*3 с повышением уровня печёночных ферментов. Полиморфные варианты CYP3A4*22 ассоциировались с более высокими уровнями интерлейкина-6. Для оценки возможностей персонализации противовирусной терапии COVID-19 требуются дополнительные фармакогенетические исследования.