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Pharmacy & Pharmacology

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Vol 12, No 2 (2024)
https://doi.org/10.19163/2307-9266-2024-12-2

RESEARCH ARTICLE 

92-104 83
Abstract

The effectiveness of the antihypertensive therapy may be associated with genetic factors that affect not only the degree of a blood pressure elevation but also predetermine an interindividual variability in response to the antihypertensive treatment.

The aim of the work was to study pharmacodynamic indices of the effectiveness of therapy with angiotensin II receptor blockers (ARBs) in the form of monotherapy and as a part of combined drugs in patients with an arterial hypertension (AH) depending on genetic features of patients – a polymorphism of the gene encoding aldosterone synthase, the C-344T polymorphism.

Materials and methods. The study included 179 patients of the Moscow region with a newly diagnosed 1–2-degree AH (141 (78.8%) women and 38 (21.2%) men) aged from 32 to 69 years who had been randomly allocated to treatment groups with irbesartan and valsartan in the form of the mono- or combined therapy with hydrochlorthiazide by simple randomization. After 3 weeks of pharmacotherapy, the presence of the genetic rs1799998 (C-344T) polymorphism of the aldosterone synthase gene, CYP11B2, and the minimum equilibrium concentration of angiotensin receptor blockers (ARBs) were determined.

Results. TT homozygotes in the irbesartan group were characterized by a lower level of the blood pressure (BP) target achievement after 3 weeks of pharmacotherapy and a higher frequency of the need to intensify the antihypertensive therapy compared with CT and TT genotypes. Among the patients taking valsartan, the carriers of the TT genotype were characterized by a higher frequency of achieving the target BP after 3 weeks of pharmacotherapy compared to the CC (p <0.001) and CT genotypes (p=0.084). Herewith, at the end of the study, according to the results of the office BP measurement and daily BP monitoring (DBPM), the achievement of the target BP values was not significantly associated with CYP11B2 C-344T genotype in both irbesartan (p >0.999) and valsartan (p=0.149). There was a trend toward a slightly more pronounced decrease in the daytime HR in the heterozygotes receiving irbesartan by a mean of 1.9 bpm compared to the CC homozygotes (p=0.059). The CT heterozygotes taking valsartan, were characterized by a less pronounced decrease in the HR by a mean of 1.4 bpm compared to the TT homozygotes (p=0.045). Moreover, the minimum drug concentration was not a statistically significant mediator of the effects (p=0.484 and p=0.736, respectively).

Conclusion. When personalizing the AH therapy in the patients of the Moscow region, to optimize the achievement of the target BP, the carriers of the TT genotype C-344T on the CYP11B2 gene should be recommend valsartan as the starting therapy of ARBs in the form of the mono- or bicomponent therapy depending on the AH degree.

105-116 49
Abstract

One of the leading mechanisms for the development of a severe cardiovascular pathology is the intensification of free radical processes. With a decrease in the activity of the antioxidant defense, the accumulation of free radicals in the body and, as a consequence, the development of the oxidative stress is natural. The registration of the severity of processes that impair the effectiveness of the antioxidant protection, with the subsequent development of an oxidative stress, can serve as a new reliable method for assessing the degree of a myocardial damage.

The aim of the work was to develop a method for assessing the degree of ischemic and ischemia-reperfusion kinds of damage to the myocardium based on the activity of free radical processes in cardiomyocytes.

Materials and methods. All the experimental work under in vivo conditions was performed on 50 white sexually mature mongrel male rats. The physiological and morphological parameters of the hearts, biochemical parameters and the lipid peroxidation level of the perfusate were assessed. The changes in the level of the perfusate lipid peroxidation were assessed in a simple model system simulating the lipid peroxidation. The registration of luminescence was carried out using a chemiluminometer KHLM-003 (Russia). Luminol (5-amino-2,3-dehydro-4-phthalazinedione) was used to detect the reactive oxygen species.

Results. With an increase in the ischemia duration and, as a consequence, the degree of the myocardial damage, an increase in the values of the lipid peroxidation determined by chemiluminescence is observed. When simulating 30 minutes of ischemia, necrosis is formed; it accounts for 8.9% of the total heart volume. With an increase in the ischemia duration to 60 minutes, the necrosis zone increases by 1.4 times (p <0.05), and the light sum of luminescence increases by 9.4% (p <0.05) relative to the 30-minute ischemia. A maximum decrease in pH is recorded at the 5th minute of the reperfusion. Next comes the restoration of pH values, and at the 10th minute, there is no longer any statistical difference between the initial and reperfusion values (7.37 vs 7.04 at p >0.05). In turn, the activity indicators of cytolysis enzymes (lactate dehydrogenase [LDH] and creatine phosphokinase-MB [CPK-MB]) show a similar pH trend of the growth in the first minutes of the reperfusion, followed by a decrease in the initial values, which is most likely due to the “washing out” of metabolic products. At the same time, the “freeze–storage (14 days)–defrost” cycle does not affect the indicator of the lipid peroxidation activity.

Conclusion. A new method for assessing a myocardial damage during the perfusion of an isolated heart using the Langendorff method, based on the use of the luminol-dependent iron-induced chemiluminescence of the lipid peroxidation level of the perfusate obtained before and after the perfusion of an isolated heart, can become one of the most effective methods for assessing the damage to the myocardial structure.

117-130 42
Abstract

Promising metabolites of potato tuberosum (Solanum tuberosum L., f. Solanaceae) are α-solanine, α-chaconine and their aglycone solanidine.

The aim of the work was to develop and validate methods for a quantitative analysis of α-solanine, α-chaconine and solanidine in dry extracts from the potato tuber peels by a high-performance liquid chromatography with a tandem  mass-selective detection (HPLC/MS/MS).

Materials and methods. The analysis was performed in a gradient mode on an Ultimate 3000 chromatograph (ThermoFisher, USA) with a TSQ Fortis tandem mass-selective detector and a 4.6 mm×100 mm, 5 μm, 100 Å UCT Selectra C18 column. An electrospray in a positive ionization mode was used in this work. The following mass transitions were used for the quantitative analysis: α-solanine, 868.4→398.3 m/z; α-chaconine, 853.4→706.3 m/z; solanidine, 398.3→98.1 m/z. The following mass transitions were used for the internal standard fexofenadine: 502.3→171 m/z and 502.3→466.2 m/z. The analysis time was 10 min. The developed chromatography conditions were validated for a suitability. The validation was performed according to the following parameters: specificity, analytical range, linearity, correctness, precision and a lower limit of quantification.

Results. The validation procedure showed that the methodology was selective, sufficiently sensitive for α-solanine, α-chaconine and solanidine (lower limits of the quantification were 50, 10 and 2 ng/mL, respectively), the linear in the concentration range of 50–5000, 10–5000 and 2–100 ng/mL, respectively; it was satisfactorily correct (RSD did not  exceed 7% for each of the substances) and sufficiently sensitive (RSD for α-solanine did not exceed 5%, for α-chaconine and solanidine – not more than 10%).

Conclusion. A technique for a quantitative determination of α-solanine, α-chaconine and solanidine in dry extracts obtained from potato tuber peels by HPLC/MS/MS has been developed and validated. This technique can be used in the routine practice of the glycoalkaloids quantitative determination when analyzing their content in food products and combination medicines.

131-149 35
Abstract

The higher education system is becoming more and more competitive every year. It faces ambitious tasks of training highly qualified personnel and ensuring technological sovereignty. A labor market analysis is an integral component of the early career guidance work with students and their navigation in the profession, which is especially important at the beginning of their employment.

The aim of the work was to conduct a comparative analysis of supply and demand indicators in the labor market of pharmaceutical specialists in nine Russian regions in 2019–2022.

Materials and methods. The research methodology included the collection, quantitative and qualitative analyses of the data on the SuperJob.ru website. The posted offers (vacancies) and CVs were analyzed on the portal SuperJob.ru (a large online service of CVs and vacancies from direct employers, agencies, employment centers) for 2019–2022 in nine regions and federal districts of Russia: Moscow and the Moscow region, St. Petersburg and the Leningrad region, the Central Federal District (without the Moscow region), the Northwestern Federal District (without the Leningrad Region), the Volga Federal District, the Urals Federal District, the Siberian Federal District, the Far Eastern Federal District, the Southern and North Caucasus Federal Districts.

Results. The analysis of the number of posted vacancies and CVs in the recruitment agency database for 2019–2022 shows a stable shortage of pharmacy professionals with both secondary (vacancies / CVs – 42112 / 41037) and higher professional education (vacancies / CVs – 36432 / 25149). The pointed out specialists are among the most required ones by employers, and pharmacy is one of the most popular areas for candidates. Cities with a high level of economy and population experience a greater deficit in specialists with pharmaceutical education. Salary levels of specialists with higher or secondary education are almost comparable on average from 50 to 75 thousand rubles, but employers generally prefer to hire specialists with higher education.

Conclusion. On average in the regions, the demand for specialists with higher education is lower than the demand for specialists with secondary education and the salary expectations of pharmacists coincide with the employers’ offers, while the salary expectations of specialists with higher education are higher in the market. Specialists with secondary education are much more numerous, as they are trained by a much larger number of educational institutions. For pharmacy technicians, a pharmacy is often the only place of work in their specialty, while for pharmacists it is usually a starting point.

REVIEW 

150-171 44
Abstract

The aim of the work was to search and analyze works on pharmacokinetic (PK) and pharmacodynamic (PD) parameters of spiramycin, allowing to evaluate the potential of this macrolide in the therapy of community-acquired infections.

Materials and мethods. The abstract databases of PubMed, Google Scholar, EMBASE, the ResearchGate scientific information network and elibrary.ru were used to search for the materials. The following key queries were used in the work: “pharmacokinetics of spiramycin”, “pharmacokinetic parameters of spiramycin”, “pharmacodynamics of spiramycin”, “mechanism of action of spiramycin”, “targets for spiramycin”, “pharmacodynamic effects of spiramycin”. The search depth – 69 years (1955–2024), the total number of publications included in the literature review in the areas of “pharmacokinetics” and “pharmacodynamics” was 72. The total number of the sources used in the article amounted  is 152.

Results. With the spread of the antibiotic resistance (AR) among the pathogens of both nosocomial and community-acquired infections, it is important for physician to search for strategies to preserve the possibility of using first-line antibacterial drugs (ABDs) in patients with infectious diseases. Spiramycin has been characterized by a minimal consumption by the population in the last decades, thus, it has a potential for the therapy of infectious diseases. The analysis of the PK spiramycin parameters indicates the ability to form effective concentrations in various tissues and organs, as well as a minimal risk of drug interactions that can alter the therapeutic response. The evaluation of its antibacterial activity in vitro and in vivo yields different results, indicating the ability of the drug to exhibit significantly greater efficacy in vivo. This paradox may be based on pleiotropic effects of spiramycin involving both host cells (immunomodulatory and anti-inflammatory effects, the ability to favorably affect the tissue regeneration, the antitumor activity, the inhibition of adipogenesis) and pathogen targets (the ability to reduce the virulence of P. aerugenosa, the antiviral effect, the reduction of the adhesion ability of cocci).

Conclusion. The PK and PD parameters and the properties of spiramycin along with the results of the published clinical studies evaluating its efficacy indicate that, despite its lower in vitro activity, the presence of additional pleiotropic effects may be the key to its superiority over the traditional macrolides in in vivo methods.

172-194 215
Abstract

In the formation of a common market within the framework of interstate associations (Unions), the goal of improving the health of the member states population can be achieved, among other things, by providing an unimpeded access to safe, effective and quality medicines (drugs). One of the elements is activities in the field of these medicinal products  compounding. This review has been prepared by authors due to the lack of information in the Russian-language literature  on the regulation of this area in the current legal systems of the BRICS countries.

The aim of the work was to analyze the regulatory mechanisms and current approaches to the organization of activities in the field of medicinal products compounding, presented in the legislation of the BRICS interstate association (Union) member countries, including their structuring (systematization) in order to develop proposals for the convergence of these practices.

Materials and мethods. PubMed, Google Scholar, elibrary.ru, and specialized databases of regulatory legal documents of the BRICS countries were used as search resources. The following keywords were used as search keywords: “drug”, “drug product”, “medicinal products compounding”, “pharmacy organization”, “medical organization”, “compounding”, “drug preparation”, “drug dilution (reconstitution)” in English, Portuguese, Spanish, Chinese and Arabic. The paper uses empirical, theoretical, quantitative tools, including the analysis of a wide list of relevant sources - regulatory legal documents governing the activities of compounding pharmacies in the BRICS countries.

Results. The study presents key regulatory legal acts and documents, analyzes them and describes the main provisions of the legislative framework for the organization of activities in the field of medicinal products compounding. The identified peculiarities determine the need to rethink the current state of the Russian regulation of the medicinal products compounding sector. The study emphasizes the need to improve regulatory approaches in Russia. The BRICS countries can strive to develop the best practices and “gold” standards for the organization of this socially important activity in the field of medicinal products compounding. Such an approach can led to the creation of a unified good practice in compounding and dispensing of medicinal products.

Conclusion. The authors of the study consider it advisable to carry out a further and more detailed elaboration of the convergence issues of regulatory practices of both health care systems and pharmaceutical industries in the BRICS member states. It has been proposed to develop and form a “Roadmap” (an action plan) for the development of the cooperation between the BRICS member states in the field of health care and pharmaceutical industry in order to intensify integration processes and build a modern model of the public health and drug market, including joint research and development by world-class scientific centers for technological development of the interstate association (Union) countries.



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ISSN 2307-9266 (Print)
ISSN 2413-2241 (Online)