ADRB2 gene polymorphism and preterm labor

This article discusses issues related to the role of polymorphism of the ADRB2 gene encoding β2-adrenergic receptor in preterm labor and tocolysis. Information is provided on scientific studies related to the search for associations of the carriage of alleles and genotypes of ADRB2 with the preterm labor, as well as with the pharmacological response to tocolytic therapy using β2-adrenergic agonists. The history of the discovery of the relationship of ADRB2 gene polymorphisms with preterm labor is presented in chronological order. As scientific facts emerge, researchers are faced with the question: how can ADRB2 gene polymorphisms affect physiological processes? That is, whether they affect by changing the primary structure of the receptor or by changing the level of expression. Depending on the answer to this question, pharmacogenetics are faced with a further task: what to study - individual polymorphisms or haplotypes?

Pharmacogenetics of antiviral agents for the treatment of COVID-19

Presented a literature review on the possible influence of pharmacogenetic markers on the efficacy and safety of COVID-19 therapy. Clinical studies of remdesivir and favipiravir are reviewed. Potential pharmacogenetic markers are described based on the available data on the pharmacokinetics of the drugs. We separately described the effect of the infectious-inflammatory process on the expression of cytochrome family enzymes.

Importance of using a pharmacogenetic approach to predict individual pharmacokinetics and safety profile of apixaban

In recent years, there has been a trend towards increased prescribing of direct-acting oral anticoagulants (DOACs) due to favourable pharmacokinetics and pharmacodynamics without the need for regular coagulation monitoring. However, recent studies have documented individual variability in plasma DOAC levels. DOAC pharmacogenetics is a relatively new area of research. There is a need to understand the role of pharmacogenetics in the adaptation of anticoagulant therapy according to a patient’s genetic characteristics. This scientific review of current data on the impact of different gene polymorphisms on apixaban pharmacokinetics broadens the understanding of the clinical relevance of genotyping for treatment efficacy and safety.

Safety assessment of a new anti-tuberculosis drug in silico and with the participation of healthy volunteers

Relevance. In connection with the increase in the number of cases of multidrug-resistant tuberculosis (MDR-TB), the search for new anti-tuberculosis drugs (ATD) is necessary. The assessment of its effect on the human body outside the aspect of the therapeutic effect is one of the main directions in the development of anti-TB drugs.Aim. Evaluation of the possible toxicity of thiosonide, a new domestic anti-TB drug, combining a consistent study of this side of the drug using a bioinformatics approach and an analysis of the results of a clinical safety study.Methods. The bioinformatic assessment was carried out using web services and models to predict the toxicity of thiosonide. The safety assessment in relation to healthy volunteers was carried out as part of a clinical study according to the protocol: «An open-label study of the pharmacokinetics, safety and tolerability of the drug thiozonide, capsule 100 mg with a single dose of increasing doses by various groups of healthy volunteers.» (2013, Permit No. 187 to conduct a clinical trial dated March 22, 2013, issued by the Ministry of Health of the Russian Federation).Results. Potential unwanted targets were identified, the predicted activity value for which was greater than 7. The results obtained indicate the likelihood of the effect of thiosonide on these protein targets and, possibly, the ability of the latter to cause side effects associated with changes in the activity of these molecules. The cytotoxic and carcinogenic effect of thiosonide is not predicted. During a clinical study, the drug thiosonide showed good tolerance and safety, since the identified adverse events did not show a definite or reliable relationship with the study drug. The resolution of all adverse events was complete, and dose escalation did not affect the number, severity of AEs and association with the study drug.Conclusion. The safety analysis of thiosonide demonstrated its good tolerability both during in silico assessment and in a study with the participation of healthy volunteers.

Personalized pharmacotherapy of arterial hypertension patients with musculoskeletal system diseases based on pharmacogenetic aspects

Pharmacotherapy in patients with comorbidity is a current issue for clinical practice. Combination of hypertension and musculoskeletal diseases can be found in 40% of outpatients, which requires simultaneous administration of different drugs. The main mechanisms of drug interactions are associated with pharmacokinetics or pharmacodynamics alterations. It has been proven that changes in drugs pharmacokinetics can be due to cytochromes P450 activity. The main symptom of musculoskeletal diseases is chronic pain, which requires long-term therapy with non-steroidal anti-inflammatory drugs (NSAIDs). The 2C19 isoenzyme takes part in metabolism of some NSAIDs. Losartan, the inhibitor of renin-angiotensinaldosterone system (RAAS), is also metabolized by the 2C9 isoenzyme and is quite often prescribed to outpatients to treat hypertension. Hence, an influence of genetic factors on efficacy and safety of antihypertensive drugs and NSAIDs combinations requires further studies.

Oncobox molecular profiling for a patient with recurrent endometrial cancer

Relevance. Endometrial cancer (EC) is the most common gynecological tumor. As a rule, it has a good prognosis, but in case of relapse, it worsens significantly. The effectiveness of cytotoxic chemotherapy for the treatment of such patients remains low.Purpose. To present a clinical case demonstrating the possibilities of therapy performed according to the results of molecular profiling of the tumor by RNA sequencing methods.Methods. Analysis of the anamnesis data, the results of histological and immunohistochemical studies, PET-CT, ultrasound images, and RNA sequencing data was carried out. The results of therapy prescribed in accordance with the rating of targeted drugs obtained after processing the transcriptomic profile by the Oncobox diagnostic platform were evaluated.Results. After experimental second-line therapy, a partial response was recorded.Conclusion. Early molecular profiling and therapy assignment in accordance with its results can change the course of the disease and improve the quality of life of patients.

Клинический случай персонализации терапии варфарином: фармакогенетическое тестирование и межлекарственное взаимодействие

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Влияние полиморфизмов гена CYP2C9 на гипотензивный и гипоурикемический эффекты лозартана

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Исследование роли мутации в гене SLC6A1 в развитии шизофрении in vitro

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Влияние носительства клинически значимых аллельных вариантов генов CES1, PON1, ABCG2, CYP4F2, CYP3A4, IGTB3, P2Y12, PEAR1, B4GALT2 на антиагрегантное действие клопидогрела и клинические исходы пациентов с ОКС и фибрилляцией предсердий

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