The aim of the work was to compare the effects of ademethionine, acetylcysteine and taurine on the zoosocial behavior of rats in a post-intoxicated state after an acute ethanol poisoning.

Materials and methods. The study was conducted on male rats of the Wistar line. The post-intoxication state was modeled by a single injection of ethanol (3 g/kg, intraperitoneally). 30 min after awakening, the animals were injected with a physiological solution, acetylcysteine (1 g/kg), ademetionine (100 mg/kg) or taurine (40 mg/kg). A zoosocial interaction test was performed 30 min after the administration.

Results. Among the behavioral indicators investigated, the following were validated: the number of acts of freezing, their duration, the number of acts of sniffing in front, the number of acts of avoidance and the number of vertical stances without support (p <0.05 between the values of the negative and positive control groups in all cases). The administration of acetylcysteine, ademetionine and taurine reduced the number of freezing acts by 53.64, 7.27 and 24.51%, respectively (p <0.05 when compared with the indicator index in the animals from the positive control group in all cases). The administration of acetylcysteine and taurine reduced the number of avoidance acts by 50 and 10%, respectively (p <0.05 when compared to that of the animals from the positive control group in both cases). All amino acids normalized the communicative performance, although it did not differ from that of the animals from the positive control group (p >0.05). Alcoholization reduced the number of vertical stances by 65% (p <0.001 when compared with that in the animals from the negative control group), and when followed by the administration of ademetionine and taurine, the reduction was 38 and 36%, respectively (p <0.05 when compared to that in the animals from the negative control group).

Conclusion. According to the data obtained, sulfur-containing amino acids, primarily those that had central effects, normalized neuronal functions, positively influencing a complex behavior of rats. Taking into account the results of the previous studies, it was possible to conclude that the therapeutic effect of ademetionine and taurine in the context of a post-intoxication state is mediated by their central effects, which are not so pronounced in comparison with acetylcysteine.

The accessibility and pharmaceutical care coverage are linked to political, economic and managerial decisions. That fact necessitates the evaluation of the state programs results in the field of the drug provision.

The aim of the work was to assess the quantitative results of the implementation of the High-Cost Nosologies program in the Russian Federation from 2008 to 2023 to determine further vectors of its improvement.

Materials and methods. The regulatory base of the work was made up of the Russian Federation legislation in the field of the drug provision. The open sources were used as the research information base for the data collection and analysis: reports of federal and regional executive authorities, materials of specialized conferences, results of published studies.

Results. The drug coverage under the High-Cost Nosologies (VZN) program is provided for 14 nosologies, 11 of which are classified as orphan diseases. Since its implementation, the HCNs program has been expanded twice by including new nosologies in 2019 and 2020. As of 01 October 2023, the number of patients in the Federal Register of VZN was 263 721 people, which was 13.58 times greater compared to 2008. The drug provision is carried out according to the list of 47 INNs. The amount of funding for the program increased from RUB 32 bn in 2008 to RUB 87.96 bn in 2023. The most resource-intensive nosologies include hemophilia, multiple sclerosis and oncohematology.

Conclusion. The main quantitative characteristics of the implementation of the HCNs program and the identified vectors for its further improvement have been analyzed in this study. The results obtained can be used to conduct analytical studies, including the ones within nosologies and nosological groups included in the program, in order to optimize a pharmaceutical care. The focus of improving the implementation of the VZN program is related to the improvement of the legal framework, a patient treatment paradigm and approaches to its financing.

Tamsulosin is a first-line drug in the treatment of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). Despite high estimates of its efficacy and safety, it rates may vary due to genetic polymorphisms of genes for the enzymes involved in the drugs metabolism.

The aim of the work was to evaluate the carriage influence of genes polymorphisms of the CYP3A enzymes group of tamsulosin metabolizers on the efficacy and safety of therapy in patients with LUTS in BPH.

Materials and methods. A total of 142 patients with LUTS, with an established BPH diagnosis (N40 according to ICD-10) were included in the study and underwent all stages. All patients received monotherapy with tamsulosin 0.4 mg/day for at least 8 weeks. An IPSS questionnaire with the definition of quality of life, a prostate ultrasound with the determination of the prostate volume and residual urine, as well as uroflowmetry, were used to evaluate the results of the treatment. Controls were performed at 2, 4 and 8 weeks from the start of the therapy. The carriage of polymorphic markers CYP3A4 (*1B, *22) and CYP3A5*3 was determined in patients; HPLC was used to determine drug concentrations in blood plasma and levels of cortisol and its metabolite 6-beta-hydroxycortisol in urine to assess the phenotypic activity of CYP3A.

Results. No statistically significant associations between CYP3A phenotype (defined by CYP3A4 and CYP3A5 genotypes) and clinical parameters of the tamsulosin therapy efficacy and the safety assessment in the studied sample of patients were found (p >0.05). Similar data were obtained for individual variants of CYP3A4*1B, CYP3A4*22, CYP3A5*3 (p >0.05). The comparison of the tamsulosin residual equilibrium concentration values in patients in the study sample with respect to the carriers of CYP3A4 and CYP3A5 gene variants did not reveal the presence of significant differences in either CYP3A phenotypes  and carriers and non-carriers of individual CYP3A4*1B (p=0.57), CYP3A4*22 (p=0.37) and CYP3A5*3 (p=0.76) variants. No association was found between the metabolic ratio of 6-beta-hydroxycortisol / cortisol in urine and the CYP3A phenotype encoded by a combination of genotypes of CYP3A4 and CYP3A5 gene variants (p >0.05).

Conclusion. A possible association between the carriage of CYP3A4*1B, CYP3A4*22, CYP3A5*3 variants, a CYP3A activity assessed by the content of an endogenous substrate of this isoenzyme and its metabolite in urine, the level of plasma concentration of the drug, and the efficacy and safety of tamsulosin, has not been confirmed. The contribution of CYP3A4 and CYP3A5 genetic polymorphisms to clinical parameters of the tamsulosin therapy requires a further study.

A quantitative assessment of nitric oxide (NO) production in body tissues is an urgent problem in pharmacology and biochemistry. The study of physiological processes occurring with the participation of NO, as well as the metabolism and pharmacodynamics of pharmacological agents from the group of NO donors, requires the introduction of accurate and reproducible methods for the quantitative determination of this metabolite in biological media.

The aim of the study was to develop the HPLC-MS/MS methods for the quantitative determination of NO in various tissues of rats.

Materials and methods. The indirect NO quantification was based on estimation of the level of more stable metabolites: nitrites and nitrates extracted from rat tissues by homogenization with water. The reduction of nitrates to nitrites was carried out using nitrate reductase. The derivatization of nitrites was based on a reaction with Griess reagent. The resulting azo dye was determined by HPLC-MS/MS using an Agilent InfinityLab Poroshell 120 EC-C18 4.6×100 mm, 2.7 μm analytical column. The total chromatographic analysis time was 12 minutes, and the analyte retention time was 6.1 minutes. The analytical range of the method was 0.1–100.0 nmol (in terms of nitrite) per 1 ml of plasma or tissue homogenate.

Results. The developed a bioanalytical method was validated according to the following parameters: a selectivity, a matrix effect, a recovery degree, a sample transfer, an analytical range linearity, a lower limit of quantification (LLOQ), an intra- and inter-assay accuracy and precision, and a stability at all the stages of the analysis. To test the method, the NO content in the plasma, brain, heart, aorta and lungs of rats was determined.

Conclusion. The developed bioanalytical HPLC-MS/MS methods fully meets the validation requirements. The metrological characteristics of the technique make it possible to highly accurately estimate the NO production in various tissues of rats, which is undoubtedly relevant and in demand in the study of pathological processes as well as the mechanism of action of pharmacological agents from the group of NO donors.

The aim of the work was to study the influence of the researcher on the muscle strength assessment in animals in the experiment by comparing the results of the automated “inverted grid” test and its classical variant.

Materials and methods. Male lines (Bla/J, n=20; FUS(1-359), n=20; Tau P301S^+/+, n=20) and their background controls (C57BL/6J, n=20; CD1, n=20) were selected for the study. The dynamics of changes in the muscle deficit of the animals was evaluated in the automated and classical variant of the “inverted grid” test.

Results. According to the results of the muscle strength assessment of mice with an edited genome of lines FUS(1-359)^+/-, Tau P301S^+/+, B6.ADysf^prmd/GeneJ, using the “inverted grid” test in the classical variant and the automated one, it was found that statistically significant differences were not obtained in comparison with the results obtained by the classical variant of the test. The standard error of the mean increases by 23–39% in the classical test compared to the automated one. It was shown that the standard error of the mean in the classical variant of the test in Tau P301S^+/+ mice was 6.24; 5.94; 5.88; 7.38 at 4 age points; in FUS(1-359)^+/- mice, 4.49; 6.8; 6.98 and 4.1; B6.ADysf^prmd/GeneJ mice, 7.66; 7.58; 8.3 and 7.92, respectively.

Conclusion. Thus, the value of the standard error of the results study mean of the changes dynamics in the muscle strength when using the automated variant of the “inverted grid” test was reduced in comparison with the results of the classical variant of the test. The results of the study show that the automation of generally recognized behavioral tests is able to increase the accuracy of the obtained data reducing the influence of a human factor on the manipulation.

The aim of the study was to analyze the literature sources for pharmacodynamic and pharmacokinetic features of gabapentin, providing its use in patients with neuropathic pain, as well as a comparative evaluation of its efficacy and safety when used in different doses.

Materials and methods. PubMed, Google Scholar, EMBASE, ResearchGate scientific information network and elibrary.ru databases were used as search resources. The keywords used for the search were “gabapentin”, “mechanism of action”, “gabapentin targets”, “gabapentin pharmacodynamics”, “pharmacokinetics”, “pharmacokinetic parameters”, “neuropathic pain”, and “randomized clinical trials”. The depth of the search was 26 years (from 1998 to 2024). This review resulted in 87 literature sources.

Results. Neuropathic pain (NeP) is one of the most common types of chronic pain, characterized by a high prevalence among people of the working age. Effective pharmacotherapy aimed at eliminating the pain syndrome is a key tool for improving the quality of life and preserving the work capacity of patients. Heterogeneity of etiologic factors involved in the genesis of NeP indicates the need to use drugs the analgesic effect of which is based on weakening the transmission of pain impulses in the CNS. In clinical trials, gabapentin has demonstrated efficacy in reducing the severity of pain in patients with postherpetic NeP, painful diabetic neuropathy and many other conditions accompanied by NeP. The dose of gabapentin 300 mg/day is the initial dose in the therapy of NeP and requires a further slow titration depending on the patient’s response to therapy and tolerability of the drug, especially in elderly and senile patients, as well as in patients with an impaired renal function. According to the published data, the most pronounced analgesic effect is achieved in the patients against the background of the gabapentin administration at a dose of 3600 mg/day.

Conclusion. Gabapentin is the drug of choice in the management of patients with NeP of different etiology and intensity. A satisfactory safety profile and pharmacodynamic effects make gabapentin possible, despite the long history of its use, to remain a relevant drug used by a wide range of physicians, specialties, for pharmacotherapy of NeP patients.