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The article (the third one of authors cycle of historical studies of medication supply and pharmaceutical business) examines period of economic renaissance of the Russian pharmaceutical market in the first years of third millennium. The state of market according data of Russian analytical agencies, medical periodicals and recollections of participants is considered. The article consists of three reports. In the first report the issue was the “field players” of pharmaceutical market, and in the second one - all the personnel serving market game, making it possible, their reflections on their new, post-Soviet experience of life in private business.

Nirmatrelvir is an antiviral drug that, in combination with ritonavir, is an effective agent for the etiotropic therapy of patients with mild to moderate COVID-19.The aim of the study was to evaluate bioequivalence of the generic drug nirmatrelvir Аrpaxel in combination with ritonavir and the original drug Paxlovid, which is a combination of nirmatrelvir/ritonavir, in a single dose administration to healthy volunteers.Materials and methods. This research was an open-label, randomized, two-period crossover bioequivalence study. It included 2 periods, in each of which the volunteers received either a test drug (nirmatrelvir at the dose of 300 mg) in combination with ritonavir (100 mg), or a reference drug (a combination of nirmatrelvir 300 mg and ritonavir 100 mg), given as a single dose. A wash-out period between each of the administrations was 7 days. The blood sampling to determine the concentration of nirmatrelvir was carried out in the range from 0 to 36 h in each of the study periods. A nirmatrelvir concentration was determined by a validated HPLC-MS/MS method with a lower quantitation limit of 10 ng/mL. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00–125.00%.Results. In the study were included 68 healthy volunteers, 67 participants of which were included in the bioequivalence population. The pharmacokinetic parameters of the drugs were comparable to each other. The 90% confidence interval for the ratio of the geometric mean of the maximum drug concentration in the blood plasma and the area under the pharmacokinetic curve «concentration-time» from zero to the last blood draw within 36 hours of nirmatrelvir was 87.26–100.83 and 93.27–103.74%, which meets the criteria for assessing bioequivalence. The test drugs were well tolerated by the volunteers. The incidence of adverse events was similar for the test and reference drugs. No serious adverse events were recorded during the entire study.Conclusion. As a result of this study, bioequivalence of the test and reference drugs has been established.

Background. Interleukin (IL) 6 plays an important role in the pathogenesis of comorbid rheumatoid arthritis (RA) depression, and IL-6 inhibitors (i) used to treat RA patients may have an antidepressant effect.Objective – to evaluate the effectiveness of Russian iIL-6 olokizumab (OKZ) in reducing symptoms of depression in patients with moderate/high RA activity.Material and methods. To date, 49 RA patients have been included, of which 43 (87.7%) are women, with an average age of 47.8±12.8 years; with a predominant high activity of RA according to DAS28 (CRP) indices (89.8%), SDAI (79.6%) and CDAI (75.5%) and inefficacy of stable 12-week therapy of сDMARDs. In all patients, a psychiatrist, in accordance with ICD-10, diagnosed depression (chronic or recurrent) of varying severity during a semi-structured interview. At week 0, all patients were randomized by the method of sequential numbers in a ratio of 1:1:1 to one of the 3 study groups: group 1 – cDMARDs+OKZ 64 mg subcutaneously once every 4 weeks (n=18); group 2 – cDMARDs+OKZ 64 mg subcutaneously once every 4 weeks + psychopharmacotherapy (PPT) (n=26); group 3 – cDMARDs+PPT (n=5). The duration of the study is 24 weeks. The dynamics of depression severity was assessed on the PHQ-9, MADRS scales; anxiety – HAM-A; experimental psychological projective techniques were also used.Results. After 12 and 24 weeks of therapy, there was a significant decrease in the severity of depression and anxiety in all groups of patients. However, the difference between the final and initial values of all scales was statistically significantly greater (pPHQ-9 24–0 =–6.75±3.91; ΔMADRS 24–0 =–22.5±4.83; ΔHAM-A 24-0 =–14.6±5.37) and cDMARDs+PPT (ΔPHQ-9 24–0 =–15.5±3.53; ΔMADRS 24–0 =–25.0±1.41; ΔHAM-A 24-0 =–18.5±3.53), compared with the cDMARDs+OKZ group (ΔPHQ-9 24–0 =–4.00±3.89; ΔMADRS 24-0 =–5.75±8.29; ΔHAM-A 24–0 =–8.50±8.21). According to a semi-structured interview with a psychiatrist and design experimental psychological techniques, the proportion of patients without depression after 24 weeks of therapy was significantly higher in the groups of patients receiving PPT: 90% in the group of cDMARDs+OKZ+PPT and 100% – cDMARDs+PPT, as opposed to 25% in the group of cDMARDs+OKZ. OKZ therapy contributed to the normalization of night sleep but did not lead to a decrease in the frequency and severity of cognitive disorders (CD).Conclusions. OKZ has an antidepressant effect in RA patients, leads to a decrease in the frequency of sleep disorders, but a com[1]plete regression of depression symptoms is possible because of the appointment of OKZ without PPT only in 25% of RA patients, mainly in patients with mild depression. Optimal for the complete regression of depression, anxiety and a decrease in the frequency and severity of CD is a combination of OKZ and PPT.

Molnupiravir is one of the drugs for the etiotropic therapy of a new coronavirus infection COVID-19. It has confirmed its clinical efficacy in the treatment of patients with mild and moderate COVID-19, including those who are at high risk of progressing to severe disease.The aim of the study was to evaluate bioequivalence of the generic drug molnupiravir ALARIO-TL and the original drug Lagevrio with a single oral administration in healthy volunteers.Materials and methods. This bioequivalence study was an open, randomized, two-period crossover study. In each of the two periods, volunteers received a single dose of the test drug, or reference drug molnupiravir, in the form of capsules at the dose of 200 mg. The washout period between the doses was 3 days. To determine pharmacokinetic (PK) parameters and bioequivalence, the concentration the concentration of N-hydrozycytidine (NHC), the main molnupiravir metabolit in the blood plasma of volunteers was evaluated. The blood plasma sampling was carried out in the range from 0 to 16 hours in each of the study periods. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00 – 125.00%.Results. A total of 28 healthy male volunteers were included in the study. According to the results of the statistical analysis, after the administration of the test and reference drugs, the 90% CIs for the ratio of the geometric means of AUC (0–16) and Cmax were 96.31% – 113.64% and 91.37% – 114.8%, respectively. These intervals fit within the established limits of 80.00–125.00%, which confirms the bioequivalence of the drugs. When comparing the frequency of the individual adverse events registration, no significant differences were found out after the administration of the test and reference drugs.Conclusion. Based on the results of this study, it can be concluded that the test and reference drugs of molnupiravir are bioequivalent. In addition, the data obtained indicate that the drugs have similar safety profiles.

The article (third one out of author's cycle of historical studies of medicinal provision and pharmaceutical business) considers period of economic renaissance of Russian pharmaceutical market during the first five years of Third Millennium. The market conditions are analyzed according data of Russian analytical agencies, materials of medical periodicals and memories of participants. The article is composed of three reports. The first report demonstrates changes in composition of essential players on market field that occurred after 1998 default.В данной статье (третьей из авторского цикла исторических исследований лекарственного обеспечения и фармацевтического бизнеса) рассматривается период экономического ренессанса российского фармацевтического рынка в первые 5 лет третьего тысячелетия. Авторы анализируют состояние рынка по данным российских аналитических агентств, материалам медицинской периодики и воспоминаниям участников. Статья состоит из трех сообщений. В первом сообщении показаны изменения в составе основных игроков на рыночном поле после дефолта 1998 г.

In a series of articles, researchers analyze the significance of the 1998 default for the development of the pharmaceutical industry and for the fates of pharmaceutical market participants. The second communication presents the results of an analysis of predictive statements and the collective memory of representatives of the pharmaceutical community. The analysis was carried out on the basis of the interviews published in pharmaceutical publications and taken by the authors of the article during 2019-2021. A total of 43 texts were used.

The article opens series of publications devoted to the history of occurrence of pharmaceutical market in Russia. The specifics of medication supply system in the Soviet period, circumstances of its deconstruction in early 1990s and modes of overcoming medication scarcity in 1993-1994 are considered. The authors compared publicly available digital data of 1990s documenting state of pharmaceutical branch, with testimonies of pharmaceutical market participants, their speculations on its state and conceptions about its normativity. This kind of methodological approach permitted to discover latent incentives and hidden obstacles in the history of Russian Pharma and to discern asymmetries of infrastructural development.

The article proceeds to explore history of the pharmaceutical branch in the 1990s. The changes in system of medicinal supply in Russia are demonstrated through infrastructural transformations and their assessment by political figures and regulators of pharmaceutical market.

The third report, which is a continuation of article on the Russian pharmaceutical branch in the 1990s, analyses corresponding conceptions of internal observers (participators of production and distribution of medications), including their assessments of normality of emerging market. The conclusion is made that the Russian pharmaceutical market grew from chaos that resulted from wreckage of the Soviet medication supply system in 1994-1998. The general dominance of generics over patented medications, distributors over manufacturers, weak interest of state authorities to long-term cooperation with pharmaceutics for the sake of development of own national production, low legal culture were generic characteristics of its infrastructure.

The researchers, in series of articles, analyze significance of the default of 1998 for both pharmaceutical industry and participants of pharmaceutical market. The Report I presents results of investigation of corresponding economic and social aspects of issue. The article presents contradictions in tax and financial policies of then ruling authorities; regulatory drawbacks created by inefficient awareness of economic situation and social specificity of pharmaceutics; means for pharmaceutical companies to survive in these conditions.

In recent years in medical educational process new innovative technologies are widely used with computer simulation, providing the reality of medical intervations and procedures. Practice-training teaching with using of simulation allows to improve the efficiency of learning material at the expense of creating imaginary professional activity and leading barring material to practical activity. The arm of the investigation is evaluation of the students training efficiency at the Medical Institute on the topic "General Anesthesia with using a modern simulation "SimMan 3 G". The material of the investigation is the results, carried out on the basis of the Centre of Practical skills and medical virtual educational technologies (Simulation Centre) at the Medical Institute of NEFU by M.K. Ammosov. The Object of the investigation was made up by 55 students of the third (3) course of the Faculty of General Medicine of the Medical Institute of NEFU. The investigation was hold during practical trainings (April-May 2014) of the General Surgery Department on the topic "General Anesthesia". A simulation practical course "General Anesthesia" consisted of 12 academic hours. Practical training was carried out using instruments, equipments and facilities to install anesthesia on the SimMan 3G with shooting the process and further discussions of the results. The methods of the investigations were the appreciation of students background knowledge before and after practical training (by 5 points scale) and the analysis of the results. The results of the investigation showed that before the practical course only 23 students (41.8%) had dot positive marks: "Good"--7 students (12.7%) and "Satisfactory"--16 (29.1%) students. The rest 22 (58.2%) students had bad results. The practical trainings using real instruments, equipments and facilities with imitation of installation of preparations for introductory anesthesia, main analgesics and muscle relaxants showed a patients reaction on the virtual trainer SimMan 3 G. Students were divided into anesthetic team, co-assisting of an anesthesiologist, an assistant and nurses anesthetist, who conducted general anesthesia (the mask anesthesia, intravenous anesthesia, endotracheal anesthesia). After finishing the practical course 16 students (29.1%) got 5 marks (Excellent), 35 students (63.6%)--4 (Good) and 4 students (7.3%)--3 mark (Satisfactory).