Today the activities of compounding pharmacies in terms of the drug compounding and in-pharmacy packaging of approval drugs is considered as a priority social task of the Russian Federation, due to the need to solve problems that are aimed at ensuring the strategic independence of the state from external and internal challenges, as well as threats, widespread introduction of personalized pharmacotherapy methods, opportunities in the field of optimizing the costs of the healthcare system.

The aim of the study was to conduct a historical analysis and comprehensive review of the current state of legal and regulatory framework of the Russian pharmaceutical market in the field of compounding drugs, as well as to develop proposals for improving the regulatory field.

Materials and methods. The following methodological tools – empirical, theoretical, quantitative ones – have been used in the work. In particular, an analysis of a wide range of relevant sources of information was carried out and information was obtained from legal and regulatory framework for the activities of compounding pharmacies in the Russian Federation, which was implemented using a bibliometric method of analysis.

Results. The main elements of the Russian legislation in the field of drug circulation with the aim of a comprehensive understanding of the classification and determination of the role of extemporaneous drugs in the Russian healthcare system, are presented in the article. A historical and technical analysis of the regulatory practice development is consistently presented. The key issues of organizing the pharmaceutical business in the field of compounding and dispensing of drugs on the territory of the Russian Federation have been considered, and current problems that need to be solved when improving the regulatory field, are presented.

Conclusion. The review conducted makes it possible to clarify further actions to improve federal legislation and delegated legislation in the field of circulation of compounded drugs by pharmacy organizations. The work presents recommendations that will contribute to the development of compounding pharmacies in the constituent entities of the Russian Federation.

The aim of the work is to conduct a review of medications approved by the FDA in 2022.

Materials and methods. In searching for the materials to write this review article, bibliographic databases including PubMed, Google Scholar and e-library.ru were utilized. The search was conducted for the publications spanning the period from 2008 to 2023. Herewith, the following keywords and word combinations were used: new drug approval, NDA, drug authorization, approval package, breakthrough medicine.

Results. The discovery and development of medications are among the most crucial scientific processes in healthcare. Developing a new drug is a highly intricate, expensive, and time-consuming process. Nowadays, the problem of costs reduction and the process of expedited discovering of new medications are particularly pertinent. To optimize the search for active compounds, virtual and high-throughput screenings, machine learning, artificial intelligence, cryo-electron microscopy, and drug repurposing are employed. Simultaneously, the search for original molecules to serve as the basis for innovative drugs continues. This article presents a review of medications approved by the FDA in 2022 for the treatment of various pathologies.

Conclusion. A drug development is a complex and resource-intensive process, with only a small fraction of candidates advancing to clinical trials. A drug design evolves in tandem with societal needs, and this review highlights some of the medications approved by the FDA in 2022. Technological advancements are expected to expedite drug development, potentially reducing the time to the market. Biotechnology, including cell therapy, holds significant prospects, and achievements in genetic mapping and chip technologies will enhance the accessibility of personalized pharmacology.

The aim of the work was to evaluate the GABA neuroprotective properties and its structural analogues in old animals after seven months of hyperglycemia.

Materials and methods. Diabetes mellitus was modeled in white outbred male rats (12 months old) by the administration of a streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg) combination. After 6 months, the animals with a postprandial glycemia level between 11 and 18 mmol/l were selected for the study. After the groups had been formed, the animals were administrated with GABA and GABAergic compounds (Compositions МРВАand PPC), respectively, for 1 month, the control group animals were administrated with saline. After the treatment, an oral glucose tolerance test and a set of behavioral tests aimed at studying sensory-motor (Open Field, Adhesion test, Rotarod) and cognitive functions (New Object Recognition and Morris Water Maze), as well as the functional state evaluation of the endothelium were performed. Further on, sampling of blood and brain tissues for a biochemical and enzyme immunoassay (the level of glucagon-like peptide-1 (GLP-1) and TNF-α in serum and the level of Klotho protein, BDNF, Nrf2, NF-κB and malondialdehyd (MDA) in brain homogenates), as well as a morphological analysis of changes in CA1 and CA3 neurons of the hippocampus and somatosensory cortex, was carried out.

Results. GABA and compositions with its derivatives had a pronounced neuroprotective effect in old animals with prolonged hyperglycemia. The hypoglycemic effect of the studied compositions was accompanied by an increase in the production of GLP-1. In the animals with DM, after 6 weeks of the test substances administration, higher rates of sensory-motor and cognitive functions and a less structural damage to the sensory-motor cortex and the brain hippocampus were recorded. These effects may be due to higher levels of the Klotho proteins, Nrf2 and BDNF, as well as lower levels of NF-κB, which may underlie the suppression of the oxidative stress, the reduction of MDA and inflammation (TNF-α).

Conclusion. After 6 weeks of the administration, GABA and its compositions in old animals (19 months old) significantly improved sensory-motor and cognitive functions, reduced negative structural changes in the hippocampus and somatosensory cerebral cortex.

Remdesivir is a drug widely used for the etiotropic treatment of COVID-19. According to a number of studies, the incidence of adverse reactions during remdesivir therapy reaches 66%, with the most common is an increase in liver function tests.

The aim of the work was to study the influence of clinical, demographic and pharmacogenetic factors on the development of drug-induced liver damage during remdesivir therapy in COVID-19 patients.

Materials and methods. The study comprised 100 hospitalized patients treated with remdesivir. The patients were divided into two groups: group 1 (n=32) – remdesivir therapy, developed an increase in the level of liver transaminases; group 2 (control, n=68) – did not develop this adverse reaction. The patients in both groups underwent a pharmacogenetic study, and a retrospective analysis of medical records was performed. Based on the data obtained, the association of clinical, laboratory, pharmacological and pharmacogenetic parameters with the development of drug-induced liver damage during remdesivir therapy was studied.

Results. In the group of patients with the development of drug-induced liver damage, people with a high body mass index were significantly more likely than in the control group (30.7±4.2 kg/m² in group 1 vs. 27.3±5.5 kg/m² in group 2, p=0.003), with a history of diabetes mellitus (odds ratio (OR)=2.647, 95% confidence interval (CI)=1.092–6.414, χ²=4.785, p=0.029), with higher levels of ferritin in the blood (724.03±432.27 and 553.19±358.48 mg/mol, respectively, p=0.040), receiving therapy with angiotensin-converting enzyme inhibitors (OR=5.440, 95% CI=2.160–13.699, χ²=14.027, p=0.000), statins (OR=3.148, 95% CI=1.307–7.581, χ²=6.795, p=0.009), and also being heterozygous for the polymorphic marker rs776746 of the CYP3A5 gene (OR=3.961, 95% CI=1.343–11.686, χ²=6.772, p=0.009).

Conclusion. A high body mass index, a history of diabetes mellitus, high levels of ferritin in the blood, concomitant therapy with angiotensin-converting enzyme inhibitors and statins, as well as a carriage of the AG genotype for the polymorphic marker rs776746 of the CYP3A5 gene increase the likelihood of developing drug-induced liver damage during remdesivir therapy. In this regard, it is necessary to consider these factors when prescribing remdesivir therapy, conduct a more careful monitoring of clinical and laboratory indicators of liver damage, and develop personalized approaches to the treatment of COVID-19 patients.

The aim of the study was to determine biotransformation products of a new selective carbonic anhydrase II inhibitor – 4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide.

Materials and methods. The study was conducted on 3 Wistar rats and 3 rabbits of the Soviet Chinchilla breed. The suspension of the drug was administered intraperitoneally to rats at a dosage of 20 mg/kg, to rabbits - at a dosage of 1.6 mg/kg. The animal blood samples were collected before the administration and 1, 2, 4, 24 h after. Urine sampling was also performed in the rats before the administration and in the intervals of 0–4, 4–8, 8–24 h after. The identification of metabolites in blood, urine and plasma was carried out using HPLC-MS/MS. Poroshell 120 C 18 column (50×3.0 mm, 2.7 µm) with a Zorbax Eclipse Plus C18 pre-column (12.5×2.1 mm, 5.0 µm) was used for the chromatographic separation. The assumed metabolites were synthesized, their structure was confirmed by the NMR spectroscopy method and a high-resolution mass spectrometry. The obtained substances were compared with the substances identified in biological fluids by retention time, the main MRM-transitions and mass spectra.

Results. The N-hydroxymetabolite was revealed in the analyses of plasma, blood and urine samples which had been formed by the addition of an oxygen atom to the drug molecule. Chromatographic peaks of this compound were identified at the MRM-transitions of 255→159, 255→117, 255→89 m/z at the 7.2nd min of the analysis. The N-oxide of 4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide and N-hydroxy-4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide were synthesized; potentially, they could have been obtained during the biotransformation. During the confirmatory HPLC-MS/MS tests based on the coincidence of the retention times, the main MRM transitions and mass spectra, the ratio of the peak areas at the identified metabolite it was established that an N-hydroxy derivative. Chromatographic peaks of the N-oxide detected in the analysis of the model mixtures of the standard substance at the MRM-transitions of 255→175, 255→133, 255→89 m/z at the retention time of 5.43 min, were absent in the animal samples.

Conclusion. The studied drug is metabolized to form a single metabolite of N-hydroxy-4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide. This compound was found in freshly collected samples of biological fluids of both animal species. The structure of the metabolite was confirmed by the HPLC-MS/MS-method by comparison with the synthesized standard substance.

Liraglutide is one of the analogues of the incretin hormone human glucagon-like peptide-1 (GLP-1) and is currently a priority treatment for diseases such as type 2 diabetes mellitus (mono- and combination therapy), obesity and overweight in the presence of at least one concomitant disease.

The aim of the work was to assess the bioequivalence and comparability of the safety and tolerability profile of the drug Enligria® (liraglutide 6 mg/ml, Promomed RUS LLC, Russia) and the drug Saxenda® (liraglutide 6 mg/ml, Novo Nordisk AS, Denmark) after a single dose in healthy volunteers.

Materials and methods. This study was an open-label, randomized, crossover comparative study to evaluate pharmacokinetic parameters, safety, tolerability and immunogenicity. The study comprised 26 healthy volunteers, 26 of whom were included in the bioequivalence assessment population. The study consisted of 2 periods, in each of which the volunteers received either the test drug (liraglutide at a single dose of 0.6 mg) or the reference drug (liraglutide at a single dose of 0.6 mg) once. The washout period between each dose was 7 days. Blood plasma samples were taken to determine the concentration of liraglutide in the range from 0 to 72 hours in each study period. Liraglutide concentrations were determined using a previously validated enzyme-linked immunosorbent assay (ELISA) method. A quantitative determination of antibodies to liraglutide in the blood serum samples was carried out using a microplate photometer and ready-made ELISA kits pre-validated by the manufacturer. The conclusion about the equivalence of the compared drugs was made based on the ratio of the parameters C_max, AUC_0→t and AUC_0→t of the studied drug in relation to the reference one.

Results. The pharmacokinetic parameters of the drugs were comparable to each other. The resulting 90% confidence intervals for the ratio of the values of C_max, AUC_0-t and AUC_0-∞ of the Russian test and reference drug were 87.18–110.46, 84.40–104.11 and 86.69–103.22% respectively, which satisfied the criteria for assessing bioequivalence. The tolerability of the drugs in the volunteers was notified as good. The incidence of adverse events was comparable for the test and reference drugs. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to russian produced liraglutide were detected in the blood serum of the volunteers, which indicated the lack of the drug immunogenicity.

Conclusion. During the study, the pharmacokinetic equivalence of the test and reference drugs was confirmed. The Russian drug Enligria® (liraglutide 6 mg/ml, Promomed RUS LLC, Russia) in comparison with a foreign drug Saxenda® (liraglutide 6 mg/ml, Novo Nordisk AS, Denmark).