Pharmacology & Pharmacy最新文献

{"title":"В6.А-DYSFPRMD/GENEJ MICE AS A GENETIC MODEL OF DYSFERLINOPATHY","authors":"M. V. Korokin, E. Kuzubova, A. Radchenko, R. Deev, I. A. Yakovlev, A. Deikin, N. S. Zhunusov, A. Krayushkina, V. M. Pokrovsky, O. Puchenkova, K. Chaprov, N. V. Ekimova, S. N. Bardakov, O. N. Chernova, A. Emelin, I. S. Limaev","doi":"10.19163/2307-9266-2022-10-5-483-496","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-5-483-496","url":null,"abstract":"The aim of the work was behavioral and pathomorphological phenotyping of the mice knockout for the DYSF gene, which plays an important role in the development and progression of dysferlinopathy.Materials and methods. A B6.A-Dysfprmd/GeneJ (Bla/J) mice subline was used in the work. During the study, a muscle activity was determined basing on the following tests: “Inverted grid”, “Grip strength”, “Wire Hanging”, “Weight-loaded swimming”, Vertical Pole”. Histological and immunofluorescent examinations of skeletal muscles (m. gastrocnemius, m. tibialis) were performed. The presence and distribution of the dysferlin protein was assessed, and general histological changes in the skeletal muscle characteristics of mice at the age of 12 and 24 weeks, were described. A morphometric analysis with the determination of the following parameters was performed: the proportion of necrotic muscle fibers; the proportion of fibers with centrally located nuclei; the mean muscle fiber diameter.Results. The “Grip strength” test and the “Weight-loaded swimming” test revealed a decrease in the strength of the forelimbs and endurance in the studied mice of the Bla/J subline compared to the control line. The safety of physical performance was checked using the “Wire Hanging” test and the “Vertical Pole” test, which showed a statistically significant difference between the studied mice and control. The coordination of movements and muscle strength of the limbs examined in the “Inverted Grid” test did not change in these age marks. Decreased grip strength of the forelimbs, decreased physical endurance with age, reflects the progression of the underlying muscular disease. Histological methods in the skeletal muscles revealed signs of a myopathic damage pattern: necrotic muscle fibers, moderate lympho-macrophage infiltration, an increase in the proportion of fibers with centrally located nuclei, and an increase in the average fiber diameter compared to the control. The dysferlin protein was not found out in the muscle tissues.Conclusion. Taking into account the results of the tests performed, it was shown that the absence of Dysf-/- gene expressionin Bla/J subline mice led to muscular dystrophy with the onset of the development of phenotypic disease manifestations at the age of 12 weeks and their peak at 24 weeks. Histopathological phenotypic manifestations of the disease are generally nonspecific and corresponded to the data of intravital pathoanatomical examination in diferlinopathy patients. The mice of the studied subline Bla/J are a representative model of dysferlinopathy and can be used to evaluate new therapeutic agents for the treatment of this disease.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86902999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID","authors":"G. G. Shimina, A. V. Bateneva, E. S. Tsyplenkova, S. G. Gamaley, T. I. Esina, E. Volosnikova, E. Danilenko","doi":"10.19163/2307-9266-2022-10-5-472-482","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-5-472-482","url":null,"abstract":"The aim of the work is to evaluate the hemostimulating activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) conjugates with alendronic acid (ALN) in the model of cytostatic myelosuppression and the dynamics of rhGM-CSF accumulation as a part of the conjugate in the bone tissue and bone marrow of mice.Materials and methods. The conjugates obtained by a solid-phase synthesis using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide or periodate oxidation, were used. A hemostimulating activity was evaluated in a model of a cytostatic myelosuppression induced by the administration of cyclophosphamide to CBA/Calac mice. RhGM-CSF preparations were injected subcutaneously for 4-5 days at the dose of 90 µg/kg. After the injections cycle had been completed, the total leukocyte and segmented neutrophil counts were carried out in the blood samples, and the total karyocyte count was carried out in the bone marrow samples.The tissue distribution of rhGM-CSF preparations was assessed in outbred CD-1 mice after a single intravenous administration at the effective dose. The content of rhGM-CSF in blood, femoral tissue and bone marrow was determined by enzyme immunoassay.Results. RhGM-CSF conjugates with ALN have been shown to retain the ability of the original protein to increase the number of leukocytes, segmented blood neutrophils, and bone marrow karyocytes under the action of conjugates. The stimulation of the neutrophil production used to be observed at earlier times than in the case of rhGM-CSF. The increase in the total number of bone marrow cells after the introduction of all three conjugates was more pronounced compared to the original protein (by 34%). The increased hemostimulatory effect of the AEG conjugate was accompanied by a more intense accumulation of rhGM-CSF in the bone tissue and bone marrow of mice. The rhGM-CSF introduced into the conjugate was detected in the bone tissue for 24 h and it circulated in the bloodstream for a longer time compared to the original protein.Conclusion. The data obtained make it possible to conclude that further work on the development of effective hemostimulating drugs based on rhGM-CSF conjugates with ALN, is promising.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73418206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CURRENT ASPECTS OF ETIOTROPIC COVID-19 THERAPY","authors":"D. N. Zemskov, L. Balykova, O. Radaeva, K. Zaslavskaya, P. A. Bely, Elena Semenova, M. Shirmankina, K. N. Koryanova","doi":"10.19163/2307-9266-2022-10-5-432-445","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-5-432-445","url":null,"abstract":"Since the beginning of the pandemic, repeated attempts have been made to develop etiotropic therapy for a novel coronavirus infection. Hydroxychloroquine, lopinavir/ritonavir, etc. derivatives were used as antiviral agents, however, they demonstrated a low efficiency and an insufficient safety. In this connection, other groups of drugs with a more effective and safe pharmacological profile are currently being actively used.The aim of the study was to analyze the literature references on the efficacy and safety of antiviral drugs for the COVID-19 treatment.Materials and methods. When searching for the materials for the review article writing, such abstract databases as PubMed, Google Scholar, e-Library were used. The search was carried out on publications for the period from January 2020 to september 2022. The key queries were: COVID-19, etiotropic therapy; immunological drugs; antiviral drugs; interferons.Results. Currently, there are various degrees of effective etiotropic drugs for the treatment of COVID-19 patients. The review has considered a few groups of drugs that are of interest from the point of view of etiotropic therapy: immunological drugs (anticovid plasma, the drugs based on antiviral antibodies, the drugs of recombinant interferons-α2 and -β1, as well as interferon inducers, i.e., the drugs based on double-stranded RNA sodium salt, and others); drugs that block the penetration of the virus into the cell (umifenovir); the drugs that disrupt the process of the viral replication (favipiravir, remdesivir, molnupiravir, nirmatrelvir/ritonavir).Conclusion. Synthetic antivirals, in particular favipiravir, molnupiravir, remdesivir, and nirmatrelvir/ritonavir, have the largest evidence base for their efficacy and safety. The search for new effective and safe etiotropic drugs for the treatment of COVID-19, as well as the collection and analysis of post-registration data on the drugs already used in clinical practice, continues.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83418483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CONSUMPTION DETAILS OF SYSTEMICALLY ACTING ANTIVIRAL AND ANTIMICROBIAL PREPARATIONS IN PERIOD OF NOVEL CORONAVIRUS INFECTION SPREAD IN RETAIL SECTOR OF SAMARA REGION PHARMACEUTICAL MARKET","authors":"I. Petrukhina, P. A. Lebedev, I. Sirotko, T. K. Ryazanova, E. Gladunova, A. Garanin","doi":"10.19163/2307-9266-2022-10-5-446-459","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-5-446-459","url":null,"abstract":"An analysis of the medicinal preparation consumption structure in the period of the COVID-19 pandemic in the pharmacy network reflects the existing outpatient practice and makes it possible to draw generalized conclusions about its compliance with the pharmacotherapy standards.The aim. Comparative analysis of population consumption of antimicrobial and antiviral medicines sold in the retail pharmacies of the Samara region in 2015–2021.Materials and methods. The study was conducted in the retail sector of the Samara region pharmaceutical market. The material of the study was the information on the list of items and dispensing volumes of antibacterial and individual antiviral drugs during the novel coronavirus infection spread (in 2020) in the network of the Samara region pharmacies. The data are compared with the indicators of the drug sales in 2015–2019. Methods of retrospective, comparative, graphical, methodological, content analyzes and statistical methods of analyses were used.Results. The authors have established a significant distortion in the consumption of systemic antimicrobial preparations in the Samara region pharmacy segment in the period of 2015–2019 with the predominance of the ATC (Anatomical Therapeutic Chemical Classification System) J01D group, primarily cephalosporins (38%), mainly by the parenteral administration route. The share of macrolides (J01F) consumption in volume terms was 14.9%, of fluoroquinolones (J01M) – 11.3%, beta-lactam antibiotics with beta-lactamase inhibitors – 10.7%, beta-lactam antibiotics penicillins (J01C) – 8.1%. Compared to 2019, in 2020, under the conditions of the COVID-19 pandemic, the total consumption of AMPs increased by 2.1 times. In the “Other beta-lactam antibiotics” group with a predominant proportion of cephalosporins, there was an increase by 3.2 times, in the “Macrolides and lincosamides” group – by 3.5 times, in “Quinolone derivatives” – by 2.6 times. The noted facts should be assessed as the phenomenon that can have a direct impact on the growth of an antibiotic resistance on a population scale. Among antivirals, the largest consumption increase was noted for oseltamivir and rimantadine. In absolute terms, the volume of antiviral preparations consumption in 2020 increased by 2.4 times, which was accompanied by an increase in the cost of one package by 55.8%.Conclusion. In the period of spreading a novel coronavirus infection, a significant increase in the consumption of antimicrobial and antiviral preparations (up to 20 times for certain pharmacotherapeutic groups and names) was notified, which may negatively affect the growth of the antibiotic resistance in the population.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77783432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CHARACTERISTICS OF OLOKIZUMAB PHARMACOKINETICS IN PATIENTS WITH NOVEL CORONAVIRUS INFECTION COVID-19","authors":"E. V. Tavlueva, E. V. Zernova, M. P. Kutepova, N. Kostina, V. Lesina, D. Mould, K Ito, A. V. Zinchenko, A. Dolgorukova, M. V. Nikolskaya, M. Lemak, O. Filon, M. Samsonov","doi":"10.19163/2307-9266-2022-10-5-460-471","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-5-460-471","url":null,"abstract":"The aim of the article is to study pharmacokinetic characteristics of intravenous olokizumab in patients with moderate COVID-19 to relieve a hyperinflammation syndrome.Materials and methods. The pharmacokinetic study was conducted as a part of a phase III clinical study (RESET, NCT05187793) on the efficacy and safety of a new olokizumab regimen (intravenous, at the doses of 128 mg or 256 mg) in COVID-19 patients. Plasma concentrations of olokizumab were determined by the enzyme immunoassay. The population analysis was performed using a previously developed pharmacokinetic model based on a linear two compartment.Results. The pharmacokinetic analysis included the data from 8 moderate COVID-19 patients who had been administrated with olokizumab intravenously at the dose of 128 mg. According to the analysis results in this population, there was an increase in the drug clearance, compared with the data obtained in healthy volunteers and the patients with rheumatoid arthritis: 0.435, 0.178 and 0.147 l/day, respectively. The parameters analysis within the framework of a population pharmacokinetic model showed that the main factors for the increased olokizumab clearance are a high body mass index. In addition, the presence of COVID-19 itself is an independent factor in increasing the drug clearance.Conclusion. After the intravenous olokizumab administration, an increase in the drug clearance is observed in moderate COVID-19 patients against the background of the disease course. The main contribution to the increased clearance is made by the characteristics of the population of COVID-19 patients associated with the risk of a severe disease and inflammation. When administered intravenously at the dose of 128 mg, a therapeutically significant olokizumab level was maintained throughout the acute disease phase for 28 days.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80339503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CONVENTIONAL APPROACHES TO THE THERAPY OF HEREDITARY MYOPATHIES","authors":"M. Pokrovsky, M. V. Korokin, A. Krayushkina, N. S. Zhunusov, K. Lapin, M. O. Soldatova, E. A. Kuzmin, O. Gudyrev, I. S. Kochkarova, A. Deikin","doi":"10.19163/2307-9266-2022-10-5-416-431","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-5-416-431","url":null,"abstract":"The aim of the work was to analyze the available therapeutic options for the conventional therapy of hereditary myopathies.Materials and methods. When searching for the material for writing a review article, such abstract databases as PubMed and Google Scholar were used. The search was carried out on the publications during the period from 1980 to September 2022. The following words and their combinations were selected as parameters for the literature selection: “myopathy”, “Duchenne”, “myodystrophy”, “metabolic”, “mitochondrial”, “congenital”, “symptoms”, “replacement”, “recombinant”, “corticosteroids”, “vitamins”, “tirasemtiv”, “therapy”, “treatment”, “evidence”, “clinical trials”, “patients”, “dichloracetate”.Results. Congenital myopathies are a heterogeneous group of pathologies that are caused by atrophy and degeneration of muscle fibers due to mutations in genes. Based on a number of clinical and pathogenetic features, hereditary myopathies are divided into: 1) congenital myopathies; 2) muscular dystrophy; 3) mitochondrial and 4) metabolic myopathies. At the same time, treatment approaches vary significantly depending on the type of myopathy and can be based on 1) substitution of the mutant protein; 2) an increase in its expression; 3) stimulation of the internal compensatory pathways expression; 4) restoration of the compounds balance associated with the mutant protein function (for enzymes); 5) impact on the mitochondrial function (with metabolic and mitochondrial myopathies); 6) reduction of inflammation and fibrosis (with muscular dystrophies); as well as 7) an increase in muscle mass and strength. The current review presents current data on each of the listed approaches, as well as specific pharmacological agents with a description of their action mechanisms.Conclusion. Currently, the following pharmacological groups are used or undergoing clinical trials for the treatment of various myopathies types: inotropic, anti-inflammatory and antifibrotic drugs, antimyostatin therapy and the drugs that promote translation through stop codons (applicable for nonsense mutations). In addition, metabolic drugs, metabolic enzyme cofactors, mitochondrial biogenesis stimulators, and antioxidants can be used to treat myopathies. Finally, the recombinant drugs alglucosidase and avalglucosidase have been clinically approved for the replacement therapy of metabolic myopathies (Pompe’s disease).","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85365075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MOLECULAR MECHANISMS DEFINING APPLICATION OF GLYCINE AND ZINC COMBINATIONIN CORRECTION OF STRESS AND ANXIETY MAIN MANIFESTATIONS","authors":"V. Shishkova, Y. Nartsissov, V. Titova, E. V. Sheshegova","doi":"10.19163/2307-9266-2022-10-5-404-415","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-5-404-415","url":null,"abstract":"The aim of the work was to carry out a systematic analysis of the molecular mechanisms that determine the possibility of a combined use of amino acid glycine and zinc compounds for the treatment of patients with manifestations of stress and anxiety.Materials and methods. Information retrieval (Scopus, PubMed) and library (eLibrary) databases were used as research tools. In some cases, the ResearchGate application was applied for a semantic search. The analysis and generalization of references was carried out on the research topic, covering the period from 2000 to the present time.Results. It has been shown that amino acid glycine, along with gamma-aminobutyric acid (GABA), is a key neurotransmitter that regulates physiological inhibition processes in the central nervous system (CNS) by increasing transmembrane conductance in specific pentameric ligand-gated ion channels. The introduction of zinc ions can potentiate the opening of these receptors by increasing their affinity for glycine, resulting in an inhibitory processes increase in CNS neurons. The replenishment of the glycine and zinc combined deficiency is an important element in the correction of a post-stress dysfunction of the central nervous system. A balanced intake of zinc and glycine is essential for most people who experience daily effects of multiple stresses and anxiety. This combination is especially useful for the people experiencing a state of chronic psycho-emotional stress and maladaptation, including those who have a difficulty in falling asleep.Conclusion. A balanced maintenance of the zinc and glycine concentration in the body of a healthy person leads to the development of a stable anti-anxiety effect, which is accompanied by the normalization of the sleep-wake rhythm, which makes it possible to have a good rest without any loss of working efficiency after waking up.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81538063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SYNERGIC EFFECT OF PREPARATION WITH COORDINATION COMPLEX “TRIMETHYDRAZINIUM PROPIONATE+ETHYMTH METHYLHYDROXYPIRIDINE SUCCINATE” ON ENERGY METABOLISM AND CELL RESPIRATION","authors":"M. Zhuravleva, M. Granovskaya, K. Zaslavskaya, Yu. G. Kazaishvili, V. S. Scherbakova, A. Andreev-Andrievskiy, D. Pozdnyakov, M. Vyssokikh","doi":"10.19163/2307-9266-2022-10-4-387-399","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-4-387-399","url":null,"abstract":"The article presents the results of an in vitro study of the synergetic effect evaluation of the combined preparation based on coordination complex ethylmethylhydroxypyridine succinate and trimethylhydrazinium propionate on energy metabolism and cell respiration.The aim of the study was to evaluate the mitochondria-directed action of the metabolic and antioxidant preparation based on succinic acid coordination complex with trimethylhydrazinium in relation to optimizing the energy metabolism in the cells under the oxidative stress conditions, as well as against the background of ischemic processes.Materials and methods. The study of the hydroxysuccinate complex effect of the drug Brainmax® components was carried out on isolated mouse liver mitochondria. In the course of the study, the potential of mitochondria, the generation rate of hydrogen peroxide during the respiration, the respiration rate were evaluated in the following positions: a) unstimulated by malate and pyruvate, b) stimulated by malate and pyruvate (complex I substrates), by succinate (complex II substrates), c) against the background of the initial section of the electron transport chain blockade by rotenone, d) in phosphorylation blockade by oligomycin, e) against the background of the FCCP-induced uncoupling, and f) in cyanide-blocked complex IV (cytochrome C oxidase).Results. It has been shown that the succinic acid coordination complex with trimethylhydrazinium, which is the active principle of the Brainmax® drug, significantly reduced the transmembrane potential of mitochondria (IC50=197±5 µM), compared with the widely used preparations of ethylmethylhydroxypyridine succinate and trimethylhydrazinium propionate, which facilitates the transfer of the produced ATP into the cell and preserves a vital activity of mitochondria even under stress. In the study of the mitochondrial respiration stimulated by the substrates of complex I (NADP-coenzyme Q-oxidoreductase), pyruvate and malate, the studied drug led to a more pronounced increase in the oxygen consumption with IC50=75±6 µМ. When evaluating the effect of the complex on the production of ATP by mitochondria, the most pronounced effect was observed with the addition of studied complex, which indicated to the uncoupling of respiration and oxidative phosphorylation at the given concentrations of the studied compounds. When assessing the effect of the complex on the production of hydrogen peroxide by isolated mitochondria, a significant decrease in the peroxide production was shown in the samples containing the complex of trimethylhydrazinium propionate and EMHPS.Conclusion. Based on totality of the results obtained, it can be assumed that a favorable conformation of the pharmacophore groups of ethylmethylhydroxypyridine succinate and trimethylhydrozinium propionate coordination complex included in the composition of Brainmax® leads to a synergetic interaction and more pronounced pharmacological effects on target cells. This comple","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78436836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MODERN DIRECTED ANTIVIRAL COVID-19 THERAPY: RESULTS OF MULTICENTER CLINICAL EFFECTIVENESS AND SAFETY STUDY OF FIXED NIRMATRELVIR+RITONAVIR COMBINATION","authors":"L. Balykova, N. Selezneva, E. Gorshenina, O. Shepeleva, N. V. Kirichenko, E. Simakina, K. Kolontarev, D. Pushkar, D. N. Zemskov, K. Zaslavskaya, S. M. Noskov, A. V. Taganov, P. A. Bely","doi":"10.19163/2307-9266-2022-10-4-371-386","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-4-371-386","url":null,"abstract":"The article presents the data from an open, two-stage, multicenter study on the efficacy and safety evaluation of a combined drug (a fixed combination of nirmatrelvir 300 mg and ritonavir 100 mg) in the complex therapy in COVID-19 patients.The aim of the study was to assess the safety, tolerability and pharmacokinetic parameters of the fixed combination of nirmatrelvir 300 mg and ritonavir 100 mg in healthy volunteers, the efficacy and safety assessment of the drug in the combination therapy compared with the standard therapy in COVID-19 patients.Material and methods. An open two-stage multicenter clinical study to assess the main pharmacokinetic parameters, safety, and efficacy against COVID-19 of the drug nirmatrelvir 300 mg and ritonavir 100 mg combination (Skyvira® PROMOMED RUS LLC, Russia) in the adult population, included 2 stages. At stage 1, safety, tolerability and pharmacokinetic parameters were evaluated in healthy volunteers (over 18 years of age) in order to confirm their comparability with the literature data known for a set of active substances. Phase 2 assessed efficacy and safety in COVID-19 patients. As a part of the second stage, the study involved 264 patients (men and women aged 18 to 80 years), who had been divided into two groups. The first group patients (n=132) received the study drugs (nirmatrelvir 300 mg and ritonavir 100 mg) – 1 tablet twice a day with an interval of 12±2 hours for 5 days in combination with pathogenetic and symptomatic therapy. The second group patients (n=132) received standard therapy in accordance with the approved Temporary Guidelines for the Prevention and Treatment of Novel Coronavirus Infection (Version 15 dated February 22, 2022).Results. During the study, none of the patients from the (nirmatrelvir + ritonavir) group experienced a transition of the COVID-19 course to a heavier severity level, in contrast to the patients in the standard therapy group. The study participants included patients with comorbidities (68% of the general population), with risk factors for COVID-19 progression to a heavier severity level and the risk of hospitalization (75% of the general population). There were no cases of COVID-19 progression to a heavier severity level in the study drug group. By the 6th day, in the nirmatrelvir + ritonavir group, the proportion of the patients who had achieved a complete recovery was twice more and amounted to 35.61% (p=0.0001), and the proportion of the patients with a negative RNA analysis to SARS-CoV-2 was 20% higher than in the comparison group, and amounted to 82.58% (p=0.0001). The fixed nirmatrelvir + ritonavir combination therapy has a favorable safety profile comparable to the standard therapy. The identified adverse reactions were transient in nature and did not require discontinuation of therapy or changes in the treatment regimen.Conclusion. The fixed nirmatrelvir + ritonavir combination has a favorable safety profile in COVID-19 patients, comparable to the standard the","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86938640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAFETY STUDY OF ROMIPLOSTIM BIOSIMILAR","authors":"A. N. Afanasyeva, V. Saparova, D. Karal-ogly, E. Mukhametzyanova, D. Kurkin, A. Kalatanova, I. E. Makarenko, A. Khokhlov, I. A. Lugovik","doi":"10.19163/2307-9266-2022-10-4-354-370","DOIUrl":"https://doi.org/10.19163/2307-9266-2022-10-4-354-370","url":null,"abstract":"Idiopathic thrombocytopenic purpura is a chronic autoimmune hematological disease caused by an increased destruction of platelets and associated thrombocytopenia, for the treatment of which the imported drug romiplostim is used. Сreation of the drug biosimilar provides a reduction in the cost of therapy and an access for the treatment to more patients.The aim of the study was to compare the safety indicators of the reference drug and its biosimilar in vivo and in vitro.Materials and methods. In the in vitro study, a model of “complement-dependent cytotoxicity” induced by the complement was formed on the 32D hTPOR clone 63-cell line, followed by a cell viability measurement with the CellTitter Glo® kit. An in vivo part of the study was carried out on Javanese macaque monkeys (Macaca fascicularis). During the experiment, the clinical condition, mortality, appetite of the animals, their body weight, body temperature, respiratory rate were assessed, the clinical parameters of blood and urine of the animals were also monitored, and the hemostasis indicators were additionally measured.Results. In the in vitro experiment, the original drug romiplostim and its biosimilar GP40141 were compared in terms of EC50 values. The indicatirs did not show complement-dependent cytotoxicity. According to the in vivo results, no deviations were recorded in the clinical status of the animals and their feed intake, and no lethality was fixed out in the groups either. For all the parameters studied (body weight and temperature, respiratory rate, clinical urinalysis, clinical and biochemical blood tests, coagulation hemostasis), GP40141 and romiplostim, when administered at the doses equivalent to 10 toxic doses (TDs), had comparable effects.Conclusion. In the comparison of safety performance both in vitro and in vivo, the original drug romiplostim and its biosimilar GP40141 showed similar results.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90621030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}