The aim. Development and validation of domestic software for non-compartmental analysis (NCA) of pharmacokinetic data, comparable in accuracy and functionality to the recognized foreign software Phoenix WinNonlin (USA).

Materials and methods. The PreKinetix web application is implemented in the Python programming language using the Streamlit framework. Algorithms for calculating pharmacokinetic parameters (maximum concentration [C_max], area under the pharmacokinetic curve [AUC], half-life [T_1/2], mean residence time [MRT], etc.) are based on the methods of the reference software Phoenix WinNonlin (Certara, USA), used for comparison and are widely used in international practice. Three models of single drug administration are supported: intravenous bolus, intravenous infusion, and extravascular administration. Literary and experimental data covering more than 450 pharmacokinetic profiles were used for verification.

Results. Calculations performed using PreKinetix showed complete agreement with the results of Phoenix WinNonlin with a relative error of less than 0.0001% for all main parameters. The program stably processes zero and missing values, automatically excludes incorrect records, visualizes pharmacokinetic profiles in linear and semi-logarithmic scales, and generates reports in .xlsx* and .docx* formats. The application interface allows it to be used not only by specialists but also by less trained users.

Conclusion. PreKinetix is a domestic tool for NCA that combines accuracy, automation, accessibility, and convenience. It can be used in preclinical and early phases of clinical trials, as well as in educational settings for training specialists in pharmacokinetics and biopharmaceutics.

The production of mini tablets (MTs) differs significantly from the production of regular-sized tablets and involves certain risks. The article analyzes scientific publications on the topic of MTs development and production, and based on the data obtained, assesses the risks associated with it.

The aim: To conduct a risk assessment during the pharmaceutical development of MTs.

Materials and methods. The research materials were based on the ICHQ8 guidelines for pharmaceutical development and ICHQ9 guidelines for quality risk management, State Pharmacopoeia of the Russian Federation XV edition, scientific publications on the pharmaceutical development and production of MTs. The study was conducted using the PHA (preliminary hazard analysis) method. The following were considered as critical quality attributes (CQAs) of MTs: disintegration, dissolution, uniformity of dosage units, uniformity of mass, crushing strength, and friability. Hazards were identified using the Ishikawa diagram method. Risk analysis was performed based on data from scientific publications on the development and production of MTs. Articles were searched for between 1990 and 2024 in the ScienceDirect, PubMed, Google Scholar, and elibrary.ru databases. Based on the information presented in these articles and using a logical method, the probability of occurrence and severity (consequences) of the risks were determined. Risk assessment was carried out using a risk matrix.

Results. Among the parameters of the MTs production process, the compression and mixing stages pose a danger. The compression is associated with a high risk for the following CQAs: dissolution, uniformity of dosage units, uniformity of mass, and crushing strength. Mixing is critical to ensuring dosage uniformity. Parameters of the active pharmaceutical ingredient (API), such as particle size and shape, significantly affect dissolution. In addition, the compressibility and flowability of the API are risk factors for ensuring the uniformity of dosage and MTs mass. The choice of excipients (EPs) is of great importance in the development of MTs. The type and content of the filler are of the greatest risk to the studied MTs. An irrational choice of disintegrant and anti-friction EPs can lead to impaired disintegration and dissolution of MTs.

Conclusion. As a result of the risk assessment, hazards were identified, and key risks associated with the pharmaceutical development of MTs were analyzed and evaluated. Particular attention was paid to the main groups of hazards — the influence of the properties of API, EPs, and production process parameters on MTs CQAs. It was found that during the development of MTs, the shape and size of the API particles, the compressibility and flowability of the powder mixture, the type and content of the filler and disintegrant, as well as such technological process parameters as pressing and mixing, pose a particular risk.

The aim. To evaluate the effectiveness of L-carnitine in the complex correction of cardiovascular and autonomic manifestations of long COVID in children, adolescents, and young adults.

Materials and methods. Within the framework of an open, simple, randomized, parallel-group comparative clinical study, the effectiveness of L-carnitine at a dose of 50–75 mg/kg per day in 2 doses for 6 weeks in addition to standard therapy in children and adolescents aged 10 to 17 years, as well as young people aged 18–25 years with long COVID (n = 45) was studied in comparison with the standard therapy (n = 45) using clinical and anamnestic, electrophysiological, echocardiographic and other methods. The statistical processing of the results was carried out by the variational method, and correlation and regression analysis using Student’s t-test for dependent samples, as well as the McNemar chi-square test.

Results. The most frequent clinical manifestations of long COVID were: high fatigue, headaches and muscle weakness — in 66.7–100%. After 6 weeks of treatment, the absence of complaints and normalization of objective status were noted in 93.3% of patients in the main group and 66.7% in the comparison group (p < 0.05). Repolarization abnormalities and rhythm disturbances, initially registered in 43.3% of patients, were not observed after 6 weeks of therapy in the main group, while they persisted in more than 50% in the comparison group. By the 6 weeks of treatment, there were no changes in Echo in the main group, while in the comparison group (slight dilatation of the left ventricle) persisted in 9 out of 12 patients. In the main group, according to Holter monitoring, restoration of heart rate, normalization of its autonomic regulation, reduction in the representation of bradyarrhythmias and “density” of extrasystoles were achieved.

Conclusion. The effectiveness of L-carnitine for the correction of the frequency and severity of autonomic and cardiac disorders in the subjects with long COVID has been shown.

Budget Impact Analysis (BIA) is a key step in justifying the inclusion of new medicines in the list of vital and essential medicines (VED). It allows you to predict the financial consequences of the introduction of therapy and evaluate the effectiveness of resource allocation, which is of particular importance when using innovative antitumor drugs.

The aim. Implementation of the BIA of Healthcare of the Russian Federation of the use of sonidegib to assess the feasibility of inclusion in the list of VEDs for the treatment of patients with locally advanced basal cell carcinoma (laBCCs).

Materials and methods. In the pharmacoeconomic model developed for use in the Russian Federation, the BIA was conducted for healthcare in the Russian Federation based on comparative modeling of two scenarios: basic (all patients receive vismodegib) and alternative (phased introduction of sonidegib with an increase in the share to 50% by the third year). The time horizon is 3 years. Direct medical costs, price data from VED registers, government procurement, regulatory allowances, demographic and epidemiological parameters are taken into account. Additionally, a one-way sensitivity analysis was performed in the range of ±10% of key variables

Results. An analysis of the impact on the healthcare budget of the Russian Federation showed that the inclusion of sonidegib in the list of VED will lead to a 3.15% reduction in budget costs for the treatment of patients with laBCCs (-37,270,334 rubles or -387,440.81 USD) within the modeled patient population. The presented BIA results remain stable with changes in the price of comparison drugs, the total population size and the distribution of patient flow over the years, with a deviation from the baseline value of ±10%.

Conclusion. Modeling shows that the inclusion of the drug sonidegib in the list of VED leads to a reduction in the costs of the healthcare system with a possible increase in the tolerability of therapy and an expansion of the therapeutic arsenal for the treatment of laBCCs, i.e. it is justified from the point of view of clinical and economic consequences. The results obtained confirm its pharmacoeconomic validity as an alternative to vismodegib in the treatment of laBCCs.

The aim. To evaluate the efficacy and safety of molnupiravir compared to placebo in patients with influenza and/or ARVI.

Materials and methods. The study involved 300 patients. The study included patients aged 18 to 80 years with clinical signs of influenza/ARVI (duration no more than 48 hours): elevated body temperature ≥37.5℃ and the presence of at least 2 symptoms of moderate severity (chills, headache, myalgia, sore throat, nasal congestion, runny nose, sneezing, cough, with laboratory-confirmed diagnosis of influenza/ARVI at the time of screening), meeting the selection criteria for the study. Group 1 (n=150) received the investigational medicine molnupiravir (Esperavir®, Promomed Rus LLC, Russia) 800 mg (4 capsules) 2 times/day (daily dose 1600 mg) for 5 days; Group 2 (n=150) received placebo 4 capsules 2 times/day for 5 days, then patient observation was carried out until day 14 (4 visits after screening). The effectiveness of therapy was assessed according to primary and secondary efficacy criteria. The primary efficacy criterion was the time (in days) to clinical recovery. Safety was assessed by considering the number and severity of adverse events (AEs) and serious adverse events (SAEs). For the analysis of qualitative indicators, an intergroup comparison of proportions was performed using a two-sided version of Fisher's exact test, or the χ2 ("chi-square") test. For quantitative indicators — using the non-parametric Mann-Whitney test. Differences were considered statistically significant at p <0.05.

Results. According to the results of the assessment of the primary efficacy criterion, it was shown that molnupiravir therapy statistically significantly reduces the time to clinical recovery compared with placebo (p=0.000039). According to secondary efficacy criteria, a statistically significant advantage of therapy with the investigational medicine compared with placebo was also demonstrated in terms of the frequency of patients who achieved clinical recovery at Visits 2 and 3 p=0.0110, p=0.0070), the frequency of virus elimination. Even on the 3^rd day of therapy, the frequency of virus elimination in the investigational drug group was 64.7% compared with 40% in the placebo group (p<0.0001). Statistically significant differences were also shown between the groups in the frequency of patients with the development of ARVI/influenza complications (bronchitis, acute sinusitis, pneumonia, tonsillitis, tracheitis, tracheobronchitis) by Visits 2–4 (Day 3–14) (p<0.0001), which proves the validity of using targeted antiviral therapy in relation to achieving surrogate therapy endpoints. Therapy with the investigational medicine was characterized by a favorable safety profile. The registered AEs in the molnupiravir and placebo groups belong to the category of expected and did not require drug withdrawal. No SAEs were observed during the study.

Conclusion. As a result of the phase III clinical study, the efficacy of molnupiravir (Esperavir®, Promomed Rus LLC, Russia) in the treatment of influenza and/or ARVI and the prevention of the risk of developing complications compared with placebo was proven: patients achieved clinical recovery as early as on the 3rd day of therapy. A favorable safety profile was shown, corresponding to the general characteristics of the medicine.

Related to the article: Markin S.S., Ivanov S.V., Beletsky I.P., Zakharova M.V., Ponomarev E.A., Arzamascev E.V. Assessment of the allergenic and immunotoxic properties of the recombinant non-immunogenic staphylokinase in preclinical and clinical trials. Pharmacy & Pharmacology. 2025;13(1):31-44. https://doi.org/10.19163/2307-9266-2025-13-1-31-44

We hereby inform readers that changes have been made to the final version of the article in Russian and English.

In the published article " Assessment of the allergenic and immunotoxic properties of the recombinant non-immunogenic staphylokinase in preclinical and clinical trials" the authors found an error: randomly, due to a technical error and without any malicious intent, in the "Results" section, subsection "Clinical study of the effect of recombinant non-immunogenic staphylokinase on the formation of specific antibodies and neutralizing activity of patient plasma" (p. 37, second column, 4th paragraph from the top), erroneous numerical indicators were indicated: "In the study of specific antibody titers in patients with STEMI who were administered recombinant non-immunogenic staphylokinase, it was found that 30 (30%) patients did not have specific antibodies. In 70 (70%) patients, specific antibodies were detected with a low titer — in the range of 1/100–1/800."

Correct version: "In the study of specific antibody titers in patients with STEMI who were administered recombinant non-immunogenic staphylokinase, it was found that 70 (70%) patients did not have specific antibodies. In 30 (30%) patients, specific antibodies were detected with a low titer — in the range of 1/100–1/800."

This error is technical in nature, because the abstract text displays correct data, and further in the text of the article correct data are shown: "...neutralizing activity of blood plasma of patients with STEMI who were administered recombinant non-immunogenic staphylokinase revealed that samples from 70 (70%) patients did not have neutralizing activity...".

The error does not change the essence of the data presented in the article, does not violate their perception by readers or interpretation.

The authors would like to apologize for any inconvenience.

The authors declare no conflict of interest.

The original article has been updated in the online version: https://www.pharmpharm.ru/jour/article/view/1674