The aim. To develop a method for in vitro cultivation of Corti’s organ explants using polyethyleneimine (PEI) as an adhesive substrate. The study evaluated the potential of PEI as an effective alternative to existing substrates for in vitro cultivation of inner ear samples.

Materials and methods. Explants of Corti’s organ from newborn mice (P1–P2) were used. Glass culture surfaces were treated with a PEI solution followed by treatment with fetal bovine serum. To assess the suitability of the developed explant model for ototoxicity studies, treatment with gentamicin was performed. Isoliquiritigenin was used as an otoprotector. Morphological analysis of images obtained by confocal fluorescence microscopy was conducted. The survival of hair cells after staining with phalloidin labeled with Alexa Fluor 488 was evaluated. The magnitude of stereociliary angles of outer hair cells was assessed.

Results. PEI- coating provided reliable fixation of Corti’s organ explants (up to 72 h) without signs of detachment from the culture surface. The samples maintained their attachment strength through two media changes and subsequent 16 washing cycles during fluorescent staining. Morphological analysis of the control group revealed no signs of toxic effects of PEI on hair cells. The organotypic model using PEI coating reproduced the classic pattern of gentamicin-induced ototoxicity with a basal-apical gradient of damage. For the first time, this model demonstrated the otoprotective effect of isoliquiritigenin (1 μM) against gentamicin-induced ototoxicity (500 μM), most pronounced in the middle turn of the cochlea for both inner and outer hair cells (p < 0.0001 for both comparisons with the gentamicin group).

Conclusion. The efficacy of PEI as an alternative substrate for cultivating inner ear samples has been demonstrated for the first time, showing optimal adhesive properties and no inherent toxicity. The developed method represents a promising approach for ototoxicity research and otoprotector screening.

The aim. To update approaches to the standardization of Angelica archangelica rhizomes and roots, taking into account modern requirements, during a comprehensive study.

Materials and Methods. Morphological and anatomical features of Angelica archangelica rhizomes and roots were studied using light microscopy. Luminescence of tissues and a working standard sample of the coumarins eleutheroside B1 (7-O-glucoside of isofraxidine) were studied by luminescent microscopy, and vascular structures were studied by polarization microscopy. The profile of volatile compounds of lipophilic fractions of water-alcohol extract and essential oil was determined by gas chromatography with mass spectrometric detection (GC-MS). The total coumarins content was determined by UV spectrophotometry.

Results. Rhizomes and roots of Angelica archangelica of Altai origin were studied for the first time. The most significant results were obtained at the excitation wavelengths in the range of 330 to 400 nm — light blue luminescence of phloem cells and secretion of schizogenous cavities was observed, due to substances of a coumarin nature. The expediency of using a histochemical reaction with Sudan III solution, which reveals schizogenous cavities, secretion droplets, and cell walls of vascular elements, has been substantiated. For the diagnosis of specific conducting elements in Angelica raw material (powder), the use of polarization microscopy is recommended. Using GC-MS for lipophilic fractions of water-alcohol extract and essential oil, a chromatographic profile was established, including substances of both terpene and coumarin nature: prenylated coumarin osthol (up to 49.72 %) and epilobulol (25.61 %). The total coumarin content in the studied raw material was 1.50 ± 0.08 % calculated as coumarin.

Conclusion. A comprehensive approach to the analysis of Angelica archangelica rhizomes and roots, involving the use of both widely used (macroscopic, microscopic, spectrophotometric) and limited-use (luminescent, polarization microscopy, and GC-MS) methods, forms the basis for the development of a draft new pharmacopoeial article “Angelica archangelica Rhizomes and Roots.”

The triple combination of elexacaftor / tezacaftor / ivacaftor is one of the key tools for targeted pharmacotherapy of cystic fibrosis. In the pediatric population, its use may be accompanied by a variable therapeutic response, which may be due to age-related pharmacokinetic features, as well as the influence of genetic polymorphism of biotransformation enzymes.

The aim. To analyze the pharmacokinetic parameters of elexacaftor, tezacaftor, ivacaftor, and lumacaftor in patients with cystic fibrosis, and to study the influence of various polymorphisms of cytochrome P450 genes (CYP2C6*4, CYP2C19*2, CYP2D6*4) and the UGT1A1 gene on pharmacokinetics.

Materials and Methods. The prospective single-center study included 32 patients with cystic fibrosis aged 6 to 18 years, of whom 29 received the combination of elexacaftor / tezacaftor / ivacaftor, and 3 received the dual combination of ivacaftor / lumacaftor. Analyte concentrations in plasma were determined by HPLC-MS/MS at five time points within 12 hours after drug administration. Molecular genetic analysis was performed on total DNA isolated from whole blood leukocytes using the phenol-chloroform extraction method.Results. Significant inter-individual variability in the pharmacokinetic parameters of all studied CFTR modulators was revealed. Normalized maximum concentrations of elexacaftor and ivacaftor were significantly higher in patients aged ≥ 12 years (p = 0.027 and p = 0.046, respectively). Carriage of the CYP2C9*4 (GG) genotype, associated with slow metabolism, led to a statistically significant increase in the systemic exposure of elexacaftor (p = 0.007) and ivacaftor (p = 0.034). For the CYP2D6*4 (AA) genotype, a significant increase in elexacaftor concentration 3 hours after administration was found (p = 0.041). Polymorphism of the UGT1A1 gene, including genotypes associated with Gilbert’s syndrome, did not have a significant effect on the total exposure of the studied drugs, while lower concentrations of tezacaftor and elexacaftor were noted at individual time points in carriers of the *28 allele.

Conclusion. The pharmacokinetics of CFTR modulators in children are characterized by high variability and depend on age and the polymorphism of genes encoding CYP2C9 and CYP2D6 isoenzymes. The obtained data justify the need for further research to optimize dosing, taking into account genetic and demographic factors.

The metabolic characteristics of anticoagulants largely depend on the patient’s genetic profile, determining the variability of pharmacological response to drugs and the risk of adverse reactions. Among the key genes encoding enzymes responsible for anticoagulant metabolism are CES1, CYP2C9, and VKORC1. They significantly influence the pharmacokinetics and pharmacodynamics of both indirect and direct oral anticoagulants, which dictates the effectiveness and safety of anticoagulant therapy. In clinical practice, the implementation of pharmacogenetic testing before prescribing anticoagulants will significantly reduce the risk of complications and improve therapeutic efficacy.

The aim. To assess the frequency of clinically significant polymorphisms of the CYP2C9 (rs1799853), VKORC1 (rs9912121), and CES1 (rs2244613) genes in patients residing in the Astrakhan region.

Materials and Methods. The study sample consisted of 90 patients residing in the Astrakhan region who received inpatient treatment for confirmed coronavirus infection COVID-19 and were receiving anticoagulants. Venous blood collected in EDTA tubes was examined: diagnostic kits “CYP2C9 gene Arg144Cys (rs1799853)” (NPF Sintol LLC, Russia), “VKORC1 gene G1639A (G3673A) (rs9923231)” (NPF Sintol LLC, Russia), and “CES1 gene C(-33)A (rs2244613) GenTest” (NMT LLC, Russia). After DNA isolation and amplification, blood samples were genotyped by PCR. The study was conducted with an assessment of Hardy–Weinberg equilibrium (p > 0.05).

Results. The results showed that the frequency of VKORC1 gene polymorphisms occurred in 60 (66.7%) patients (95% CI: [56.96–76.44]; p > 0.05), CES1 gene in 55 (61.1%) (95% CI: [51.03–71.17]; p > 0.05), and CYP2C9 gene in 24 (26.7%) (95% CI: [17.56–35.84], p > 0.05).

Conclusion. The obtained results revealed a high frequency of distribution of polymorphic variants of genes associated with altered pharmacological response to anticoagulant therapy in patients residing in the Astrakhan region. This highlights the potential for implementing pharmacogenetic testing in the regional healthcare clinical practice for a personalized approach, optimized dosing, and reduced risks of adverse outcomes.

The aim. To conduct a comparative evaluation of the physicochemical properties, biological activity, bioequivalence, and safety, including tolerability and immunogenicity, of the drug Semaltara® (semaglutide, tablets 3 and 14 mg (Biochemik, Russia) and the drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark) when administered to healthy volunteers.

Materials and Methods. To assess the bioequivalence of the investigational drug Semaltara® (semaglutide, tablets 3 and 14 mg (Biochemik, Russia) with a chemically synthesized active substance to the original (reference) drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark), an open-label randomized crossover comparative study (n = 110) was conducted. Patients were randomized into 4 groups: Group 1 (n = 25) — patients received the investigational drug Semaltara® and the comparator drug Rebelas® daily once a day at a dose of 3 mg (1 tablet) for 28 days; Group 2 (n = 25) — the comparator drug Rebelas® and the investigational drug Semaltara® daily once a day at a dose of 3 mg (1 tablet) for 28 days; Group 3 (n = 30) — the investigational drug Semaltara® and the comparator drug Rebelas® daily once a day at a dose of 14 mg (1 tablet) for 28 days; Group 4 (n = 30) — the comparator drug Rebelas® and the investigational drug Semaltara® daily once a day at a dose of 14 mg (1 tablet) for 28 days. The concentration of semaglutide was determined in serum samples using a pre-validated enzyme-linked immunosorbent assay (ELISA) method. The conclusion on bioequivalence of the compared drugs was made based on the assessment of 90 % confidence intervals for the ratios of geometric mean values of C_max and AUC_(0–t) parameters of semaglutide in the original units of measurement.

Results. The results of the clinical study demonstrated the bioequivalence of the investigational drug and the comparator drug. The pharmacokinetic parameters of the drugs were comparable: Based on statistical analysis, the obtained 90 % confidence intervals for the ratio of C_max,ss and AUC_(0-τ)ss values of semaglutide 3 mg were 96.57–120.94 % and 94.37–120.06 %, respectively. For the 14 mg dosage, the 90 % confidence intervals for the ratio of C_max,ss and AUC_(0-τ)ss values of semaglutide were 91.79–109.68 % and 91.47–112.80 %, respectively. The tolerability of the drugs in volunteers was noted as good. No serious adverse events were registered during the entire study. Thus, the investigational drug Semaltara®, tablets, and the comparator drug Rebelas®, tablets, have a similar safety profile, including tolerability, at both the 3 mg and 14 mg dosages.

Conclusion. The conducted study demonstrated the bioequivalence and similar safety profile, as well as tolerability of the Russian drug Semaltara® (semaglutide 3 and 14 mg, tablets, Promomed LLC, Russia) in comparison with the foreign drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark).

The aim. To evaluate the effect of semaglutide on certain cardiovascular risk factors in patients with obesity.

Materials and methods. The study included 50 individuals: men and women aged 18 to 65 years, patients with overweight (BMI ≥ 27 and < 30) and obesity (BMI ≥ 30), combined with at least one comorbidity (prediabetes or type 2 diabetes mellitus), arterial hypertension, dyslipidemia, obstructive sleep apnea syndrome, or cardiovascular disease. Patients received subcutaneous semaglutide (Velgia®) once a week. Clinical examination was performed, including: interview, blood pressure measurement, anthropometric data assessment (height, weight, BMI, waist circumference, and hip circumference), cardiovascular risk assessment using the SCORE scale, biochemical blood analysis (including lipid profile), and adverse event registration.

Results. A significant decrease in body weight, BMI, waist circumference, and hip circumference was observed after 12 weeks of semaglutide therapy. By 24 weeks, a sustained reduction in these indicators continued. After 6 months of semaglutide use, positive changes in the lipid profile were identified: a decrease in total cholesterol by 8.27% due to a decrease in non-HDL cholesterol, LDL cholesterol by 12.73 %, triglycerides by 13.09 %, and the atherogenic index by 1.83 %. Velgia® therapy for 6 months led to a reduction in the calculated 10-year cardiovascular risk according to the SCORE2 scale by 18.6 %. Analysis of anthropometric and biochemical blood data showed a significant decrease in indicators, indicating a reduced risk of cardiovascular events in patients with obesity.

Conclusion. During semaglutide therapy, no clinically significant changes were observed in liver function parameters (ALT, AST, ALP, bilirubin), pancreas (amylase), kidneys (creatinine, urea, GFR), and systemic inflammation markers (CRP). However, a significant decrease in transaminase activity (ALT, AST) and blood uric acid concentration was noted. The registered adverse events (primarily gastrointestinal: nausea, epigastric discomfort) were temporary and moderate in nature. No cardiovascular events were observed during the use of semaglutide.

The aim. To evaluate the safety profile of cefodizime in comparison with ceftriaxone and amoxicillin/clavulanic acid based on an analysis of current literature data.

Materials and methods. A literature search was conducted among randomized controlled trials, cohort studies, meta-analyses, and clinical guidelines for the period from 2021 to 2026 in the PubMed database.

Results. The analysis of publications and one clinical guideline revealed that the safety profile of cefodizime in comorbid patients is more favorable compared to ceftriaxone and amoxicillin / clavulanic acid. The use of ceftriaxone is associated with a dose-dependent and duration-dependent risk of developing biliary pseudolithiasis, cholestatic hepatitis, nephrolithiasis, and crystalluria, especially in patients with risk factors such as decompensated comorbidities, dehydration, starvation, and polypharmacy. Amoxicillin/clavulanic acid remains one of the leading causes of drug-induced liver injury, including cholestatic forms, and also demonstrates clinically significant interactions with vitamin K antagonists and direct oral anticoagulants. No convincing data on hepatotoxicity or nephrotoxicity or clinically significant interactions with oral anticoagulants were found for cefodizime, including in patients with hepatobiliary and urinary system pathology. However, the limited volume of clinical studies requires further investigation of its safety in larger cohorts.

Conclusion. Cefodizime, ceftriaxone, and amoxicillin / clavulanic acid are effective in comorbid patients; however, their safety profiles differ. Cefodizime is characterized by a lack of data on hepatotoxicity and nephrotoxicity and does not demonstrate clinically significant drug interactions with oral anticoagulants, unlike ceftriaxone and amoxicillin / clavulanic acid. At the same time, the limited number of clinical studies on cefodizime requires further investigation of its safety profile in larger cohorts of comorbid patients.