The aim. To describe the key characteristics of medical products approved by the Food and Drug Administration (FDA) and released by pharmaceutical companies from 2012 to 2024.

Materials and methods. The analysis is based on data from FDA publications related to the approval of medical products from 2012 to 2024. The products were systematized by year, pathway and reason for approval, nature of the active substance (synthetic, semi-synthetic, natural or biological) and target disease (indication for use) in accordance with the codes of the Anatomical Therapeutic Chemical (ATC) classification.

Results. During the analyzed period, the FDA approved a significant number of medicines, while maintaining a stable proportion of small molecules with a significant upward trend in the number of approved biologicals (monoclonal antibodies, CAR-T, siRNA, gene therapy, etc.). The largest proportion was accounted for by antitumor drugs and immunomodulators (group L according to ATC), demonstrating steady growth with projected growth in the future. Interest in drugs for the treatment of metabolic disorders and diseases of the nervous system remained steadily high, with the emergence of innovative therapeutic approaches. A gradual increase in the number of repositionings and extensions of indications was noted. The COVID-19 pandemic did not have a significant impact on the overall structure of approvals, and only two specific medicines for the treatment of COVID-19 were approved. There has been an increase in approvals for orphan diseases and the emergence of innovative therapeutic approaches: gene therapy, RNA interference, cell technologies, and bispecific antibodies.

Conclusion. In the period from 2012 to 2024, the pharmaceutical industry has seen a fundamental shift towards biotechnological development methods, personalized medicine, and targeted therapy. During the period under review, the proportion of small molecule approvals remained fairly stable, but a steady (compared to previous periods) increase in the number of biotechnology product approvals (monoclonal antibodies, gene and RNA therapy) can be noted. The largest increase was noted in class L (antitumor drugs and immunomodulators), which reflects the focus of global pharmaceutical companies on the fundamental study and discovery of pharmacotherapy opportunities in the oncology and immunity. It is necessary to note the trend towards the development of drugs for the treatment of rare (orphan) diseases. In the field of therapy for metabolic disorders, during the specified period, drugs were approved that revolutionized understanding of an entire cluster of diseases and approaches to therapy, and a new standard of therapy was formed due to SGLT2 inhibitors and agonists of the incretin system receptors, including molecules with a multi-targeted effect. The COVID-19 pandemic led to a limited number of drug approvals for the treatment of this infection but thanks to it, the “door” to the development of new generation vaccines has been opened, which are largely fundamentally different from those currently existing. The discovery of new means to combat infectious agents of various nature (bacteria, protozoa, viruses, fungi, and parasites) is also one of the priority goals of pharmaceutical companies, as evidenced by a significant proportion of approvals of drugs with a similar effect. In terms of “reasons for registration,” the main share fell on original drugs; the contribution of new combinations and dosage forms was at its peak in the middle of the period and then decreased. Due to the expiration of patent protection for many drugs and the accumulation of data on their effects in the post-marketing period, a gradual increase in the number of repositionings and extensions of indications can be logically noted.

Despite the proven efficacy of silodosin for lower urinary tract symptoms (LUTSs), significant interindividual variability in response to pharmacotherapy and the development of adverse events persists. Potential factors for this variability include pharmacogenetic and epigenetic mechanisms regulating drug metabolism.

The aim. To investigate the impact of CYP3A4*22 polymorphism and circulating microRNA miR-27b level on the pharmacokinetics, efficacy, and safety of silodosin in patients with benign prostatic hyperplasia (BPH).

Materials and methods. The study included 98 patients with LUTS due to BPH who were prescribed silodosin 8 mg/day for 8 weeks. IPSS and QoL dynamics, and the frequency of adverse events were assessed. The steady-state minimum concentration of silodosin (Css) was determined by HPLC-MS/MS. Genotyping for CYP3A4*22 was performed by real-time PCR. The expression level of plasma miR-27b was determined using RT-qPCR.

Results. Patients with the CT genotype (12.2%) had significantly higher Css values compared to carriers of the CC genotype (13.44 [6.35; 16.6] vs 6.15 [3.10; 11.31] ng/mL; p = 0.005717). Despite this, the reduction in symptom severity according to IPSS and improvement in QoL were comparable in both groups (p >0.05). No correlation was found between Css and IPSS dynamics (rs = -0.115554, p = 0.257195). MiR-27b levels did not differ between genotypes and did not correlate with either Css or clinical outcomes. The structure of adverse events corresponded to the established safety profile of silodosin; no statistically significant differences were found between genotypic groups.

Conclusion. Carrying the CYP3A4*22 polymorphism is associated with increased silodosin exposure, but the clinical efficacy of therapy remains independent of this genetic marker. Data on the role of miR-27b in regulating pharmacokinetics and clinical outcomes in this population were not confirmed.

The aim. Within a series of 3a,6-epoxyisoindole-2(3H)-(carbox/thio/seleno)amides, we sought to identify a multimodal scaffold suitable for the further development of agents to prevent and treat fibrotic diseases by assessing of compound’s ability to mitigate glycation and oxidative stress, key triggers of fibrogenesis; to select a non-cytotoxic lead with a balanced combination of these two activities, and to preliminarily evaluate its anti-inflammatory potential.

Materials and methods. Target 3a,6-epoxyisoindole-2(3H)-(carbox/thio/seleno)amides were synthesised using the IMDAF approach. Antiglycation activity was evaluated in a bovine serum albumin-glucose model by registering advanced glycation end-product (AGE) fluorescence. Antioxidant properties were determined using the ABTS assay. Cytotoxicity and antiinflammatory effects were studied in peritoneal macrophages from adult wild-type white mice (n = 4; body mass 30–35 g). Cytotoxicity was assessed by the MTT assay and lactate dehydrogenase (LDH) release, while anti-inflammatory effects were evaluated in a model of LPS-induced nitric oxide (NO) production.

Results. The study delineates promising directions for modifying the epoxyisoindole scaffold for drug discovery and proposes a screening framework for agents targeting pathologies dependent on non-enzymatic damaging mechanisms (glycation, oxidation), including fibrotic diseases. Active molecules were identified among derivatives of hydrogenated 3a,6-epoxyisoindole. Compound 2.10 — 7a-chloro-N-(4-chlorophenyl)-1,6,7,7a-tetrahydro-3a,6-epoxyisoindole-2(3H)carbothioamide — exhibited an optimal balance of antiglycation (at 100 μM, inhibition of glycation 40.1 ± 1.7%) and antioxidant activity (at 111 μM, reduction in ABTS•+ colour intensity 57.1 ± 1.1%) with low cytotoxicity (apparent from ≥ 250 μM). By contrast, compounds 2.16–2.19 (bearing an aroyl fragment) showed exceptionally high antioxidant activity (95.0–96.5% reduction in ABTS•+ colour intensity) without concordant antiglycation effects (inhibition not exceeding 15%). In the model used, anti-inflammatory activity of 2.10 was not detected.

Conclusion. Compound 2.10 is a promising starting point for further structural optimisation toward agents acting on early pathogenetic events driven by non-enzymatic damaging triggers, including the prevention and treatment of fibrotic remodelling.

The aim. To study the main characteristics of consumers of hypoglycemic drugs (HGD) within the framework of preferential drug provision (PDP) in the Stavropol Territory (ST). 

Materials and methods. The study was based on depersonalized information about patients with diabetes mellitus (DM) from the database of clinical and epidemiological monitoring of DM and data from the Regional Endocrinological Dispensary. Methods of comparative, retrospective, graphical analyses, grouping, and determination of average values were used.

Results. Among the beneficiaries with DM in the ST, individuals with type II DM prevail. In the type I DM group, men predominate (over 55.0%), while among patients with type II DM, women predominate (65.0%). The largest proportion among beneficiaries with type I DM is occupied by individuals from 30 to 60 years old, with type II DM, individuals aged 60 to 80 years predominate (70.44% — 2025). The increase in the number of beneficiaries with a disease duration of up to 5 years and over 10 years was noted. The life expectancy of beneficiaries with type I DM tends to increase slightly but steadily, while for patients with type II DM, it remains practically unchanged. A positive trend was noted in achieving the norm of glycated hemoglobin (HbA_1c) in beneficiaries with type I DM, and for every third patient with type II DM. For every third beneficiary with type I DM and for 70.0% with type II DM, body mass index (BMI) values are above normal. The structure of HGD consumption was determined, and changes in the ratio of the use of groups of oral HGD and individual trade names of drugs were revealed.

Conclusion. The general characteristics of beneficiaries with DM were identified, depending on its type, age and sex composition, duration of the disease, life expectancy, achievement of glycated hemoglobin levels, BMI, and the use of drugs in therapy.

Currently, there is a steady increase in the prevalence of metabolic disorders among the population of developed countries. Among them, obesity and type 2 diabetes mellitus are the most important health problems. Tirzepatide is an innovative drug that is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. The medcine is effective for the treatment of type 2 diabetes mellitus and obesity. The first drug with the active substance tirzepatide in Russia was Tirzetta® (manufacturer LLC «PROMOMED RUS»), which is the first in Russia, but not in the world. The reference drug for it is Munjaro® (INN: tirzepatide, Eli Lilly and Company, USA). To date, the question of the equivalence of these drugs has not been fully studied.

The aim. To conduct a comprehensive comparative evaluation of the reproduced drug Tirzetta® (INN: tirzepatide, manufacturer LLC “PROMOMED RUS”) and the reference drug Munjaro® (INN: tirzepatide, manufacturer Eli Lilly and Company, USA).

Materials and methods. The authenticity and quality of drugs were assessed by physicochemical methods according to the current pharmacopoeia of the EAEU. Spectrophotometry in the UV region, HPLC-MS/OF, and gel filtration chromatography were performed. The analysis of agonism to GIP and GLP-1 receptors was performed in vitro using reporter cell lines. The studies were performed in accordance with EMA, FDA, EAEU guidelines and in accordance with the current EAEU pharmacopoeia.

Results. As a result of the evaluation of the physicochemical properties of the studied series of Tirzetta® and the reference drug Munjaro®, it was found out that the absorption spectra in the ultraviolet region, the profile of related impurities and their quantitative content, the profile of high-molecular-weight compounds and their quantitative content, as well as mass spectra in all the studied series were similar. During the evaluation of the biological activity of the Tirzetta® and Munjaro® series, results were obtained that demonstrated the absence of statistically significant differences in the ability to activate GLP-1 and GIP receptors (p <0.0001). 

Conclusion. During the studies, the equivalence of the physicochemical properties and biological activity of the Russian drug Tirzetta® to the comparator drug Munjaro® was confirmed.