The safety assessment testing of drug and chemicals is carried out in accordance with the accepted requirements, taking into account the current regulatory documents. our articles are presented below.
Publications by topic:
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- Макаров В.Г., Капица С.И. Моделирование токсического воздействия различной интенсивности в эксперименте с помощью дихлоргидрина полиэтиленгликолей-9 // Модельные системы в медико-биохимических исследованиях. – Л., 1989. – С. 85-91.
- Avdeeva 0.I., Dyachyk G.I., Makarova M.N., Posysaeva E.S., Karachinskaya I.V., Makarov V.G., Panossian A.G. Study of chronic and reproductive toxicity of a new pharmaceutical phytocomplex «Adapt» // Fhytopharm. 2008. 12 th International congress. Book of Leiden. Netherlands. 1-4 July 2008. P.14
- Avdeeva O.I., Guseva S.I., Makarova M.N., Abrashova T.V., Stevanov S.Y., Abrashova T.V., Karachinskaya I.V. Evaluation for new herbal preparation with sage and echinacea extracts using method of range finding // Fhytopharm. 2009. 13 th International congress. Book of Leiden. Netherlands. 29-31 July 2009. P.78
- Krishen K.L., Azapkina A.A., Makarova M.N., Guseva S.I., Makarov V.G. Immunotoxic and immunomodulator effects of complex medication of plant origin // Fhytopharm. 2009. 13 th International congress. Book of Leiden. Netherlands. 29-31 July 2009. P.79.
- Гусева С. И., Макарова М. Н., Шиков А. Н., Пожарицкая О. Н., Авдеева О. И., Карачинская И. В., Дьячук Г. И. Применение метода DRF (dose range finding) для оценки общей токсичности лекарственного препарата на основе растительных экстрактов// Токсикологический вестник. -2009. № 5. –С. 26-30.
- Гусева С.И., Авдеева О.И., Макарова М.Н., Шиков А.Н., Пожарицкая О.Н., Карачинская И.В., Дьячук Г.И. Доклиническое изучение эмбрио-, фетотоксических свойств и влияния на генеративную функцию нового фитопрепарата // Вестник Санкт-Петербургской государственной академии им. И.И. Мечникова. -2009. №3(32). – С.143-148.
- Гусева С.И., Авдеева О.И., Карачинская И.В., Стефанов С.Ю Исследование биологического действия на организм растительного лекарственного препарата методом DRF (dose range finding). // Аннотации докладов и материалов 63-й итоговой научной конференции молодых ученых Ростовского государственного медицинского университета. – Ростов-на-Дону.: ГОУ ВПО Рост ГМУ Росздрава. – 2009. – С. 178.
- Авдеева О.И., Карачинская И.В., Стефанов С.Ю Изучение общей токсичности нового лекарственного препарата на основе шалфея и эхинацеи // Сборник научных работ студентов и молодых ученых Всероссийской конференции с международным участием «Актуальные вопросы медицинской науки», Ярославль ,22 апреля 2009 г. С. 113-114.
- Avdeeva O.I., Guseva S.I., Makarova M.N., Makarov V.G., Stevanov S. Yu., Karachinskaya I.V. Study of reproductive toxicity of the new herbal preparation with sage and echinacea extracts // Fhytopharm. 2010. 14 th International congress. Book of Leiden. Netherlands. 1-3 July 2010. P.51-52
- Дьячук Г.и., Шиков А.Н., Лапкина Г.Я., Макаров В.Г., Макарова М.Н. Методические рекомендации по доклиническому изучению безопасности и эффективности фитопрепаратов. Методическое пособие // Под ред. проф. д.м.н.Дьячука Г.И., проф. д.м.н. Макарова В.Г. – СПб: Из-во СПбГМА, 2010, 88с.
- Авдеева О.И., Макарова М.Н., Макаров В.Г., Драй Р. В., Абрашова Т.В, Дьячук Г. И. Изучение токсических эффектов высоких доз аскорбиновой кислоты // Профилактическая и клиническая медицина. – 2011. – №1 (38) С. 40 – 44.
- Makarova MN., Shikov A.N., Avdeeva O.I, Pozharitskaya O.N., Makarenko I.E., Makarov V.G., Djachuk G.I. Evaluation of acute toxicity of betulin // GA. 59th Annual Congress on Medicinal Plant research. 4- september – 9 september 2011, Antalya, Turkey. Planta Medica.-2011. – Vol.77, № 12. -1411.
- Рыдловская А.В., Авдеева О.И., Крышень К.Л., Ацапкина А.А., Макарова М.Н., Макаров В.Г. Изучение токсичности фракции лабдановых спиртов, выделенной из древесной зелени хвойных пород //Экспериментальная и клиническая дерматокосметология. -2011, №6.
- Makarenko I.E., Avdeeva O.I., Makarova M.N., Pozharitskaya O.N., Kryshen K.L. General toxicity study of the new medication based on the Schisandra chinensis seeds // Abstracts. Phitopharm. 2012. Obzory po klinicheskoj farmacologii i lekarstvennoj terapii. -2012. –Vol. 10, № 2. –M80.
- Рыбакова А.В., Авдеева О.И., Крышень К.Л., Макарова М.Н., Макаренко И.Е. Оценка острой токсичности противовоспалительного препарата Афлогилекс – раствор для инъекций 0,1% на аутбредных крысах и мышах // Материалы всероссийской молодежной конференции «Фармакологическая коррекция процессов жизнедеятельности. Доклинические и клинические исследования новых лекарственных препаратов» г. Уфа, 8-10 июля 2012 г. – С. 84-87.
- Авдеева О.И., Макаренко И.Е., Макарова М.Н., Симановская М.С. Изучение общей токсичности препаратов гопантеновой кислоты // Материалы IV съезда фармакологов России «Инновации в современной фармакологии». 18-21 сентября 2012 г., республика Татарстан, г. Казань. –М.: 2012. –С. 7.
- Дьячук Г.И., Ацапкина А.А., Крышень К.Л., Бекетова Д.Д., Макарова М.Н., Шиков А.Н., Макаров В.Г., Пирттимаа М. Оценка иммунотоксичности дистиллята торфа // Материалы IV съезда фармакологов России «Инновации в современной фармакологии». 18-21 сентября 2012 г., республика Татарстан, г. Казань. –М.: 2012. –С. 61-62.
- Дьячук Г.И., Авдеева О.И., Макаренко И.Е., Макарова М.Н., Шиков А.Н., Пирттимаа М., Питкенен П., Алакурттии С. Исследование общей токсичности субериновых кислот // Материалы IV съезда фармакологов России «Инновации в современной фармакологии». 18-21 сентября 2012 г., республика Татарстан, г. Казань. –М.: 2012. –С. 61.
- Рыбакова А.В., Авдеева О.И., Макарова М.Н., Макаренко И.Е. Изучение безопасности противовоспалительного препарата Афлогилекс-гель 0,02% // Материалы IV съезда фармакологов России «Инновации в современной фармакологии». 18-21 сентября 2012 г., республика Татарстан, г. Казань. –М.: 2012. –С. 160-161.
- A.V. Rybakova, O.I. Avdeeva , I.E. Makarenko, M.N. Makarova, V.D. Sokolov Evaluation of acute toxicity of anti inflammatory drug Aflogileks gel 0.02% in outbred rats and mice // International Bulletin of Veterinary Medicine. – 2013, №2. – Р. 59-63. SUMMARY. We studied the anti-inflammatory drug acute Aflogileks – Gel 0.02% for 60 outbred rats weighing 180-220 g and 60 outbred mice weighing 18-22, the drug was administered once intraperitoneally and once transdermal. The observation period was 14 days. In the study of acute toxicity Aflogileks gel 0.02% in the outbred mice and rats LD50 values could not be established. The study drug can be classified as Class VI relatively harmless substances on the classification of Hodge and Sterner [Full text is available in Russian].
- Патент RU 2383888 C1 Авторы: Тихонов В.П., Шевченко Т.В., Родина И.А., Белянкина Е.Ю., Плигина К.Л., Макарова М.Н., Гирина М.Б. Способ оценки раздражающего действия и активности природных, синтетических субстанций и готовых препаратов на куриных эмбрионах методом ультразвуковой допплерографии. Опубликовано 10.03.2010. Бюл. № 7.
- A.V. Rybakova, M.N. Makarova, O.I. Avdeeva, S.V. Khodko, M.A. Kovaleva. The use of laboratory animals for the study of drugs used in veterinary science and medicine: Study of weight percentages of the internal organs from the view point of the search of the target organ in evaluating toxicity // International Bulletin of Veterinary Medicine. – 2013, №2. – Р. 59-63. SUMMARY. Side effects of drugs revealed by toxicology studies on laboratory animals. The study of systemic toxicity to determine the most sensitive to the studied pharmacological substances organs and systems of the body, using a method massometrii internal organs. The analysis of this indicator in toxicological studies makes it possible to detect target organ toxicant, to identify signs of endocrine -related effects [Full text is available in Russian].
- Rybakova A.V., Makarova M.N., Pozharitsraya O.N., Makarov V.G. Assessment of irritating effects of eye drops ALLERGOSPIN 1% solution (Draize Test, draizer eye irritation test) // International Bulletin of Veterinary Medicine. – 2013, №3. – Р. 46-49. SUMMARY. The compounds of natural origin, which have a pronounced therapeutic effect and is not toxic to the cells and organs of the microorganism. The objects of research were Allergospin eye drops 1% solution obtained from the shells and sea urchin needles used as a promising means for the treatment of allergic diseases of the eye. Studied the irritant effect of eye drops Allergospin -1% solution by the method of Draize, 18 rabbits. The research resulted in irritation of eye drops Allergospin 1% solution, placebo and control data were obtained, indicating a lack of irritants in the conjunctiva, cornea and iris rabbit [Full text is available in Russian].
- Selezneva A., Rybakova A., Makarova M., Kovaleva M., Khodko S., Makarov V. Psyho-emotional state and training of laboratory rats for diagnostic procedures // International Bulletin of Veterinary Medicine. – 2013, №3. – Р. 72-78. SUMMARY. In response to the unusual manipulation and the primary interaction with the person any animal is under the stress. Reducing stress response of animals is necessary to perform diagnostic and therapeutic procedures. To this end, we have proposed a method of training animals, including sample manipulation. According to the survey the general state of the animals, individual behavior and blood pressure, the effectiveness of the proposed method of training was established. Duration of training necessary to achieve of efficiency, was 15 days [Full text is available in Russian].
- Makarenko I.E., Avdeeva O. I., Vanatiev G.V., Rybakova A.V., Khod’ko S.V., Makarova M.N., Makarov V.G. Possible ways and amounts of drug administration to laboratory animals // International Bulletin of Veterinary Medicine. – 2013, №3. – Р. 78-84. SUMMARY. Carrying out any preclinical studies accompanied by the introduction of a medicament animals. Under the conditions of a specific assessment of the pharmacological actions is mainly the use of sufficiently small amount of drugs, then the study of general toxic properties on the contrary – it is often necessary the administration of drugs to the maximum amounts. The volume of administration should not cause animals pain and suffering. Also, in recent times, due to the advent of new drugs and dosage forms, the need for targeted drug delivery, is a topical application of a more technologically advanced methods of administration, such as endotracheal, intranasal, intra-articular. These and some other routes of administration, and their maximum amounts, in Russian literature are often not described in detail. This article provides general data obtained in the course of many years of practical experience of our institute, the descriptions and the maximum possible volume of the main ways of introducing medicament [Full text is available in Russian].
- Posysaeva E.S., MakarovаM.N., Avdeevа O.I., Sedovа S.V., Rybakovа A.V., Makarov V.G. Characterization of the structure of the skeleton in rat embryos in the study of embryo toxicity of drugs // International Bulletin of Veterinary Medicine. – 2013, №3. – Р. 84-89. SUMMARY. In studies of teratogenic effects of drugs it is important to have a set of well-tracked or countable characteristics by which you can judge the presence and degree of teratogenic effects of the drug. In the present study were obtained characteristics of skeletal development in normal embryos of outbred rats (RAMS “Rappolovo”) on day 20 of gestation. It is shown that these characteristics are uniform in the submitted sample, and can serve as a starting point in evaluating the effect of drugs on skeletal development during gestation [Full text is available in Russian].
- Atsapkina A.A., Kryshen K.L., Beketova D.D., Akulova E.G., Makarova M.N., Balabanyan V.Yu., Shobolov D.L., Makarov V.G. Genotoxic properties of the quercetin in liposomal form // The 17th international congress. Phytophrm, 2013. Vienna, Austria, 8-10 July Обзоры по клинической фармакологии и лекарственной терапии. –Т. 11. –С. 10.
- Makarenko I.E., Avdeeva O.I., Pozharitskaya O.N., Makarova M.N., Shikov A.N. Acute and chronic toxicity studies of a lipid extract of green sea urchins gonads in rodents // The 17th international congress. Phytophrm, 2013. Vienna, Austria, 8-10 July Обзоры по клинической фармакологии и лекарственной терапии. –Т. 11. –С. 61.
- A. Selezneva, M. Makarova. Ethical principles for the treatment of animals in Russia // International Bulletin of Veterinary Medicine. – 2014, №1. – Р. 69-75. ABSTRACTS. Russia’s lack of documents regulating the ethical principles of the treatment of animals is the cause of the difficulties of international relations in various fields of science and animal husbandry. Matter of moral attitudes to animals is relevant throughout the world and characterizes the level of civilization of the country. In order to justify the need for the development and implementation on the territory of Russian documentary ethical bases world was made a historical overview of the emergence and development of ethical canons in the world and in Russia. As a result of literature search we have found that in the history of Russia there were only 5 regulations governing ethics in dealing with animals, and the law on the protection of animals in Russia and was not adopted. The level at which Russia is in this matter, perhaps resulting in the low credibility as scientific research, and the country as a whole. Thus, the creation of the Russian legal framework ethical treatment of animals is necessary in our opinion [Full text is available in Russian].
- А. Muzhikyan, M. Makarova, Y. Gushin. Features autopsy report of the experimental group of animals // International Bulletin of Veterinary Medicine. – 2014, №1. – Р. 75-80. ABSTRACTS. Pathomorphological examination of laboratory animals is one of the most reliable methods for detection of organ and tissues abnormalities. Description of pathomorphological changes in tissues and organs in the group of experimental animals is difficult and time-consuming task due to individual variability. To determine the cause of death, especially when the death occurred during the toxicological experiment, it is very important to consider the multiplicity of observed abnormalities. To improve the reliability of the data and to optimize data classification we have developed raw data recording forms for autopsy report. These forms allow collecting original recordings made during the course of the pathomorphological examination of the group of animals. Effective form design makes it easy to complete these forms and analyze data. Final autopsy report is based upon these forms. In contrast to traditional autopsy report, here all observed abnormalities are summarized and calculated within group of animals. These forms for raw data recordings can be successfully used in general macroscopic pathomorphological diagnostics of animals. Using these forms group differences can be easily detected. Samples of the forms for raw data recordings can be applied not only in the practice of pathology, but also in the general animal health diagnostics [Full text is available in Russian].
- A.E. Kastornova, E.S. Korotchenko, K.L. Kryshen, A.A. Atsapkina, D.D. Beketova, M.N. Маkarova. Practical guidance for immunotoxicity of new medications. Phagocytic activity of peritoneal macrophages // International Bulletin of Veterinary Medicine. – 2014, №1. – Р. 85-91. ABSTRACT. Innate immune response evaluation is one of the immunotoxicity studies of new medications. Macrophages play the key role in the innate immunity. Aim of the present study was to determine the experiment parameters of mice peritoneal macrophage phagocytosis with fluorescent latex beads. Intraperitoneal injection of 3% thyoglicollate medium was used to isolate a maximal count of macrophages. The lavage was harvested in 5 days after the stimulation. The macrophages were elicited using the adhesion. To evaluate phagocytic activity, we used latex beads, diameter 1 µm and conjugated with FITC. The incubation time periods were from 30 to 150 minutes. Calculated phagocytosis index varied from 1,14 to 1,26 and it averaged almost 0 with the use of cytochalasin D in 10 µM. So, the present metodology could be further applied to evaluation of peritoneal macrophages phagocytosis activity to study non-specific immune response and immunomodulating properties of new medicines (drugs) and substances [Full text is available in Russian].
- Atsapkina, K. Kryshen, A. Kastornova, M. Makarova, V. Makarov. Immunological status of laboratory animals under conditions simulating immediate hypersensitivity // International Bulletin of Veterinary Medicine. – 2014, №1. – Р. 91-99. ABSTRACT. A type I hypersensitive reaction is induced by certain types of antigens referred to as allergens, and has all the hallmarks of a normal humoral response, often characterized by variable airflow obstruction. The presence of airways inflammation and hyperreactivity provides further evidence for the disease. Model of immediate hypersensitivity in laboratory animals are used widely and allow to study spastic acute airway responses, airway hyperreactivity, late and early phase immunological response. Animal species selected for study have included: mice, rats and guinea-pigs. Numerous parameters can be measured in animal systems, including specific and total immunoglobulin E (IgE), pulmonary eosinophilia and diaphragm contractions. It is recognized that no single factor is sufficient to lead to a conclusion of hypersensitivity immediately type, but rather that a selected combination of parameters is most fitting. A guinea-pig system has been utilized for more than 90 yrs and has contributed to the basic understanding of physiological and immunological processes involved in allergic respiratory sensitization. The benefits as well as the disadvantages to be derived from each of the animal systems have been enumerated in this review. Attention must always be given to identifying differences which exist between animal and human systems, including morphological, physiological and immunological factors. The immunological characteristics of different species of laboratory animals, the advantages and disadvantages of their use in modeling the pathology of immediate hypersensitivity are reviewed in this paper [Full text is available in Russian].
- Selezneva, M. Makarova, A. Rybakova Randomization of experimental animals // International Bulletin of Veterinary Medicine. – 2014, №2. – Р. 84-89. ABSTRACTS. Planning of experimental research includes several key stages of sampling, determine the number of animals per group, the study parameters, study design and selection of methods of processing the results. Competent and careful planning allows to obtain reliable results that can be successfully transferred to the general population. One of the most important initial stages of this study is to randomization. Application randomization ensures representativeness of the sample as well as eliminating the probability of bias research. Randomization of experimental animals can be used a variety of methods, but methods of randomization in experimental animal studies differ from those in clinical trials. The most preferred method of distribution of the experimental animal is a block randomization method using a computer random number generator. This method allows to take into account all factors that can lead to a shift of research results, as well as to minimize the human factor [Full text is available in Russian].
- Muzhikyan, M. Makarova, Y. Gushin Features histological processing of organs and tissues of laboratory animals // International Bulletin of Veterinary Medicine. – 2014, №2. – Р.103-108. ABSTARCTS. Histological examination of organs and tissues of laboratory animals is one of the most important steps in the investigation of drug effects. It requires implementation of new approach in data collection and data analysis. The data obtained should be highly informative. It is strongly recommended to perform comparative analysis. The paper describes the methods of the preparation of histological sections which allows obtaining reproducible results. The method of data gathering and analyses is aimed to increase data validity and accuracy. Proposed technique of data collection allows identifying and quantifying between group differences. Problems typical of the method of histological examination and the measures to reduce their effect are discussed. The paper highlights the sources of artifacts that occur during tissue fixation and section. Significantly increases the accuracy and the amount of received data to objectively judge the intergroup differences in the microstructure of different animals in the experiment and have a sufficiently large amount of information on the histological structure of each animal. The ways for organ sectioning for subsequent histological processing are described. The proposed method is successfully applied in practice and can be recommended as a tool for effective and comprehensive histopathological examination of the tissue in laboratory animals [Full text is available in Russian].
- A. Atsapkina, K. Kryshen, M. Makarova, V. Makarov Bacterial test systems to evaluate the potential mutagenic effect of new drugs // International Bulletin of Veterinary Medicine. – 2014, №2. – Р. 109-113. ABSTRACT. Genetic toxicity refers to the ability of substances or physical agents to damage the DNA and/or chromosomes of cells. Such damage can lead to mutations that increase the likelihood of certain diseases, such as cancer and birth defects. Genotoxicity and mutagenicity testing are an important part of the hazard assessment of pharmaceutical compound for regulatory purposes. Genotoxicity test systems that are based on bacteria display an important role in the detection and assessment of DNA damaging chemicals. They belong to the basic line of test systems due to their easy realization, rapidness, broad applicability, high sensitivity and good reproducibility. Since the development of the Salmonella microsomal mutagenicity assay by Ames and coworkers in the early 1970, significant development in bacterial genotoxicity assays was achieved and is still a subject matter of research. The basic principle of the mutagenicity assay is a reversion of a growth inhibited bacterial strain, due to auxotrophy, back to a fast growing phenotype (regain of prototrophy). A very important aspect of genotoxicity testing is the bioactivation of drugs to DNAdamaging compounds. Most widely used is the extracellular metabolic activation by making use of rodent liver homogenates. In summary, beginning with «natural» tester strains the rational design of bacteria led to highly specific and sensitive tools for a rapid, reliable and cost effective genotoxicity testing that is of outstanding importance in the risk assessment of compounds and in genotoxicology [Full text is available in Russian].
- Авдеева О.И., Макарова М.Н., Афонькина О.В., Макаренко И.Е., Макаров В.Г., Капанадзе Г.Д. Токсикологическая характеристика антигипертензивных средств, влияющих на ренин-ангиотензиновую систему // Биомедицина. – 2014, № 2. – С. 99-104.
- Седова С.В., Авдеева О.И., Балабаньян В.Ю., Макаров В.Г., Макарова М.Н., Хамди Я.М., Швец В.И., Сравнительное экспериментальное токсикологическое исследование цитостатиков из группы таксанов и их наноразмерных лекарственных форм // Российский биотерапевтический журнал. – 2013. – Т. 12, № 4. – С. 33-37.
- Авдеева О.И., Макарова М.Н., Максименко О.О., Осипова Н.С., Балабаньян В.Ю., Гельперина С.Э. Оценка безопасности наноразмерных форм рифабутина // Фармация, 2018; 67 (5): 48–56.
- Pozharitskaya O., Shikov A., Makarov V. Toxicokinetics – methodological approaches. Laboratory Animals for Science. – 2019, №1. – P. 1-19. https://doi.org/10.29296/2618723X-2019-01-06 SUMMARY. The article discusses the importance of integration of pharmacokinetics in toxicity testing. This will be helpful in interpretation of the results of toxicological studies and ensure the development of a rational study design. The term “toxicokinetics” in the context of the development of medicines means obtaining pharmacokinetic data either as an integral component when conducting preclinical toxicity studies or in specially designed studies to determine systemic concentration. The data obtained can also be used for interpretation of the results of toxicological date and their relevance in terms of clinical safety issues. The current practice of drug development requires toxicological study from the very early stage of the search for possible candidates for drugs. Toxicokinetic studies conducted at the early stage are necessary to establish a more accurate goal in the development process. The toxicokinetic section is an integral part of the preclinical testing program and the information obtained is intended to increase the value of the toxicological data obtained, both from the point of view of understanding toxicity studies, and in comparison with clinical data as part of a person’s risk and safety assessment. Due to the inclusion of toxicity and the comparison of preclinical and clinical docie, the main focus is on the interpretation of toxicity data, and not on the characterization of the main pharmacokinetic parameters of the substance under study. The main aim of the toxicokinetic study is to determine the systemic concentrations achieved in animals and to identify their relationship with the dose level and the period of the toxicity study. In addition, when conducting toxicokinetic studies, secondary aims are: to determine the relationship between the concentrations achieved in toxicity studies and the results of toxicological studies, and to assess the compliance of the obtained data with the parameters of clinical safety; confirm the selection of the type and mode of therapy data preclinical toxicity studies; obtain information that, together with the results of toxicity studies, will allow the design of subsequent preclinical toxicity studies to be developed. Toxicokinetics also helps to select the dosing regimen and the dosing interval of drugs / chemicals necessary for successful therapy and / or experimental studies [Full text is available in Russian].
- Shekunova E.V., Kovaleva M.A., Makarova M.N., Makarov V.G. Dose selection in preclinical studies: cross-species dose conversion // Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya = Тhе Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. – 2020, 10(1). – P. 19-28. https://doi.org/10.30895/1991-2919-2020-10-1-19-28 ABSTRACT. One of the major obstacles to effective translational medicine is the challenge of translating animal research results into clinical studies. Scientific literature mainly addresses the selection of the drug dose at initiation of clinical trials (Phase 1). Appropriate selection of doses is also essential for preclinical toxicology and pharmacology studies. Some basic principles that are used when translating dosages from animal models to humans are applicable to selection and justification of doses when planning and conducting preclinical studies. The paper provides an overview of the main methods that can be used for selection and justification of animal doses in preclinical studies, e.g. cross-species dose conversion using body surface area scaling. It summarises situations when doses may be directly converted based on body weight. The paper gives special attention to cross-species dose translation according to pharmacokinetic data. There is no one-size-fits-all approach to cross-species translation; dose conversion must be scientifically justified taking into consideration all information available on the test drug, i.e. its chemical structure, intended route of dministration, pharmacokinetic parameters, preclinical and clinical data on pharmacodynamics, and inter-species differences in pharmacokinetics and pharmacodynamics [Full text is available in Russian].
- Kryshen K.L., Moshkov A.E., Demyanovskiy M.N., Kovaleva M.A. Safety Pharmacology Study of Medicines Used for Febrile Syndrome Management in Children. Safety and Risk of Pharmacotherapy. – 2020, 8(3) – P. 151-159. https://doi.org/10.30895/2312-7821-2020-8-3-151-159 Summary. Safety pharmacology studies of paediatric medicines are an important stage in the life cycle of drugs. The purpose of the study was to analyse and compare the safety pharmacology profiles of the recommended paediatric dosage regimens of a fixed ibuprofen (IBU)/paracetamol (PAR) combination and of IBU and PAR monopreparations following repeated oral administration of these products to juvenile rats. Material and methods: safety pharmacology was assessed in both male and female outbred juvenile rats. Two dose levels were used in the study—the highest treatment dose (HTD) equivalent for juvenile rats, and the three-times-equivalent therapeutic dose (3 HTD). The animals were given the fixed IBU/PAR combination in the form of suspension from dispersible tablets (100 mg IBU + 120 mg PAR), IBU in the form of oral suspension (100 mg/5 mL), and PAR in the form of oral suspension (120 mg/5 mL). Statistical processing was performed using Statistica 10.0 software. Results: unlike monopreparations, the fixed IBU/PAR combination did not have clinically significant hepatotoxic or nephrotoxic effects when administered to juvenile rats. Administration of IBU alone resulted in an increase in blood urea nitrogen concentration in female rats (HTD) and male rats (3 HTD), and a small amount of leucocytes in the urine of female rats. Administration of PAR resulted in an increase in the amount of red blood cells in the urine of male rats. Administration of the monopreparations at the HTD dose led to a decrease in the locomotor activity of the animals. No significant effect on thecardiovascular or respiratory systems was observed for any of the products. Conclusions: the safety pharmacology profile of the fixed IBU/PAR combination after repeated oral administration to juvenile rats did not differ much from those of IBU and PAR used alone, and in some cases was even better [Full text is available in Russian].