Gamma-aminobutyric acid (GABA) became known as a potentially important chemical in the brain 50 years ago, but its significance as a neurotransmitter was fully found 16 years later. It is now known that at least 40 % of the inhibitory synaptic activity in the mammalian brain is accounted for by GABA. Аim. To analyze achievements in the study of the physiological and pharmacological role of GABA receptor subtypes, their potential applications in drug development and updated information on the clinical development of subtype-selective GABA receptor compounds. Results. The GABAA-receptor complex (GABA-RC) is ligand-gated ion channels with chloride conductance. These receptors contain α, β, and γ subunits, but δ, ε, θ, and ρ can be also present. The GABA binding site is located at the interface between α and β subunits where a number of important amino acids are also found. GABA-RC is sensitive to a wide range of drugs, e.g. benzodiazepines (BDZ), which are often used for their sedative/hypnotic and anxiolytic effects. Classical BDZ interact non-selectively with α1,3,5 βγ2 GABA-RС in the binding site located at the α+γ− interface. Conclusions. In addition to the potent and rapid pharmacotherapeutic action BDZ also possess some addictive potential (drug dependence), which appears after the interaction of molecules with α1-receptors. Using the selective targeting to separate subgroups not only the main effect of BDZ without side effects can be provided, but also one can use this approach in creating new analgesic medicines; we have demonstrated it on the example of propoxazepam (full agonist GABA-R).
The main principles of creating a quality system in modern laboratory diagnostics are: standardization of laboratory processes by developing standard operating procedures; general quality management of laboratory research based on the development and implementation of the requirements of international standards (according to ISO 15189: 2015 "Medical laboratories. Basic requirements for quality and competence"); quality control of all stages of the laboratory process through the implementation of the validation procedure. Aim. To develop a methodology for conducting validation procedures to assess the suitability of a biochemical method for determining the level of total cholesterol in biological fluids in the Clinical Diagnostic Laboratory of the Clinical Diagnostic Center of the NUPh. Materials and methods. The object of the study was a standardized method for determining the concentration of total cholesterol. The method was validated using the “Cholesterol Reagent Set” test kit and the standard sample “Chemical control. Reagent kit. Level 1 ", manufactured by High Technology, Inc. (USA) with known concentration. The measurements were carried out on an Express Plus automatic biochemical analyzer manufactured by Bayer Corporation, Germany. When processing the research results, descriptive statistics were used and a number of statistical evaluations were carried out. Results. A protocol and a validation report were developed at the Clinical Diagnostic Laboratory of the CDC NUPh to assess the suitability of the method for determining the concentration of cholesterol in biological fluids by the photometric enzymatic method on an automatic biochemical analyzer Express Plus (using reagents and control material manufactured by High Technology, Inc., USA). The validation characteristics of the method were determined: repeatability and reproducibility, correctness and uncertainty of measurements. Evaluation of the internal laboratory repeatability and reproducibility of this technique indicates the absence of gross errors in the operation of the instrument and statistically important differences in measurements. The assessment of the correctness of the method (carried out using the control material) proved that the systematic error is not significant (according to a given acceptance criterion). The expanded uncertainty calculation showed that the obtained values of the total cholesterol level can be considered accurate and reliable. Conclusions. Validation of the method for determining total cholesterol in human blood by the photometric enzymatic method has proven that this method has performance characteristics that correspond to the regulated ones, meets the established criteria, and the parameters measured with it correspond to the proper ones. Key words: validation, determination method, total cholesterol, repeatability and reproducibility, correctness and uncertainty of measurements
Chlorhexidine is an effective cationic antiseptic and disinfectant that has been used in medical practice for decades. It is generally recommended to use different concentrations of aqueous or alcoholic solutions of chlorhexidine for different therapeutic purposes. Objective. To determine the proportions of different chlorhexidine concentrations in medicines purchased by state and municipal organizations and to identify possible issue of chlorhexidine formulations utilization in the suboptimal or insufficient concentrations. Results. The vast majority of the chlorhexidine-containing medicines found in the State Register of Medicines of Ukraine are 0.05% solutions for external use, 0.05% gels for dental and urological use and vaginal suppositories (pessaries) with 16 mg of chlorhexidine in one dose. While the most common representatives of chlorhexidine-containing medicines abroad are solutions with a concentration of 4% and 2%, as well as mouthwashes with a concentration of 0.12%. The highest share - 96% - among the procurements of chlorhexidine-containing medicines by state and municipal organizations is 0.05% aqueous solution for external use. Instructions for medical use of 0.05% aqueous chlorhexidine solution for external use contain indications that are not supported by international documents: WHO Model List of Essential Medicines and British National Formulary. Conclusions. The obtained results suggest probable cases of irrational use of chlorhexidine medicines in medical practice in Ukraine. The consequences of such cases are not limited to the failure to achieve therapeutic goals or to the development of nosocomial infection, but includes also the selection of chlorhexidine-resistant strains of microorganisms. Key words: chlorhexidine; assortment analysis; medicinal procurements study; suboptimal concentration; rational pharmacotherapy
Diseases of the respiratory system occupy an important place in the structure of morbidity in the population of Ukraine, being only second to diseases of the cardiovascular system in prevalence. Patients with a respiratory pathology make up a significant part of the pharmacy visitors. In most cases, at the first symptoms of such diseases, patients begin to be treated on their own with the help of non-prescription drugs, and quite often the first person they turn to is a pharmacist. A striking example of the effectiveness and safety of herbal medicine is the symptomatic treatment of cough as one of the most characteristic symptoms of the respiratory tract pathology. The use of herbal products with the antitussive, expectorant, mucolytic action has a long history, and currently it does not lose its significance. The clinical efficacy of herbal products is determined by the mechanism of their specific action, and the rational choice of the optimal drug taking into account the cause of the cough, its nature and the characteristics of the course of the inflammatory process in the respiratory organs, allows eliminating cough or effectively managing it. Bronchipret® is a herbal product of “Bionorica SE” company, which is one of the most studied and widely used in medical practice. The drug is indicated for the treatment of respiratory tract diseases accompanied by cough and sputum formation, including acute and chronic bronchitis. The main and well-studied pharmacological effects of Bronchipret® are secretolytic/mucolytic, anti-inflammatory, antiviral, antimicrobial and bronchospasmolytic ones. The pharmacological effects listed are due to a complex of biologically active substances (BAS) of such plants as the root of spring primrose, thyme herb, ivy leaf. All medicinal plants that make up the “active core” of the drug have a long history of their use in folk medicine. Moreover, their various beneficial effects on the human body in different diseases and conditions have been confirmed by empirical experience. The drug is produced in three dosage forms (drops, syrup, tablets), and it determines the targeting of its prescription to different categories of patients. The drug has a high evidence base and has been studied at the cellular and molecular levels. Conclusions. In the case of choosing a herbal medicine for responsible self-medication, drug consumers can rely on their own experience, but most of them trust the knowledge of a pharmaceutical professional, and this fact increases the pharmacist’s responsibility for the treatment prescribed. Therefore, it should be the choice of a drug with an optimal efficacy/safety ratio, which is determined from the standpoint of evidence-based medicine. It is precisely these requirements that the phytoneering drug Bronchipret® meets.
Providing the population of Ukraine with quality, effective and, at the same time, economically affordable medicines is a priority task of the healthcare system. Taking into account the relatively low cost of their development generic drugs are available to the majority of the country’s population; thus, bioequivalence studies are needed to obtain data on their efficacy and safety. Ukraine is currently in the process of harmonizing domestic regulatory requirements for generic drugs and conducting bioequivalence studies with global ones. Therefore, it is important to find out the differences in approaches to the registration of generics and studies of their bioequivalence in Ukraine and other countries. Another important aspect is to provide the policy of “transparency” of bioequivalence research results, which contributes to the use of better drugs. Aim. To analyze domestic and global approaches to the organization of the bioequivalence research and provide the policy of “transparency” of their results. Materials and methods. A comparative analysis of approaches to drug registration, requirements for generic drugs and bioequivalence studies and ways to provide the policy of “transparency” of their results in Ukraine, the United States and the European Union was conducted. Results. The analysis has revealed that the methods of registration of drugs in Ukraine, the United States and the EU are the same. Approaches to providing the “transparency” of the results of bioequivalence studies differ since in Ukraine the publication of such information is not mandatory and is at the discretion of pharmaceutical manufacturers. Conclusions. Domestic regulatory requirements for assessing generic drugs are harmonized with the world ones. Today, there is a need to introduce a mandatory requirement for the publication of bioequivalence studies, and it will contribute to providing an effective “transparency” policy.
When determining the cause of poisoning by antidepressant drugs, the data of laboratory toxicological studies of biofluids for the presence of this group of drugs are of key importance. Aim. To develop the methods for determining the antidepressant drug trazodone in the blood and urine samples using high-performance liquid chromatography with a UV spectrophotometric detection, which is suitable for analytical diagnosis of the thymoleptics intoxications. Materials and methods. The model samples of human biofluids spiked with trazodone were studied. The antidepressant was isolated from the blood and urine by the liquid-liquid extraction with methylene chloride from the alkaline medium at pH 9. Concomitant endogenous impurities were removed by extraction with diethyl ether from the acidic medium at pH 1. In the study of the blood the erythrocyte mass was pre-precipitated with the help of 10 % of trichloroacetic acid solution. Chromatographic analysis was performed on a microcolumn chromatograph using a column with a reversed-phase of C18. Results. The absolute retention time of trazodone in extracts from the model samples of biofluids was 17.91±0.09 min. The quantitative content of trazodone was determined at 250 nm by the calibration dependence of the chromatographic peak area on the concentration (μg/ml) y=(1.74∙10-3±1∙10-5)x. Under the indicated extraction conditions, 35±4 % and 78±4 % of trazodone were isolated from the blood and urine, respectively. Conclusions. The methods of trazodone isolation from the biofliuds by liquid extraction followed by the determination of the drug by high performance liquid chromatography with a multiwave UV spectrophotometric detection have been developed. The methods are recommended for using in the practice of forensic and clinical toxicology.
The high incidence of malignant tumors is currently supported by the general ageing of the world population and unfavorable environmental factors. In 2018, 18.1 million new cases of cancer and 9.6 million deaths from them were registered in the world. At the same time, a significant increase in the life expectancy of these patients after the treatment noted over the past 20 years highlights the problem of side effects of the anticancer therapy. One of the most serious side effects is the development of doxorubicin-induced cardiomyopathy (DRIC). In all three distinct clinical forms (acute, early and late) DRIC can develop in 58 % of patients after using anticancer treatment regimens with the inclusion of doxorubicin. The review provides a detailed analysis of medicinal treatment regimens and preparations (ACE inhibitors, beta-blockers, statins, etc.) currently used, and evaluates their effectiveness and expected results. Currently, several therapeutic strategies have been proposed for the prevention and treatment of DRIC, each of them has certain positive results. At the same time, some therapeutic methods used in the clinic have some disadvantages. Conclusions. The limitations of the results of DRIC prevention achieved by the existing therapeutic regimens, as well as the possibilities for their prediction, have been stated. The need for further research to improve the effectiveness of medicinal prevention and treatment of DRIC is emphasized.
The rational treatment of acute rhinosinusitis of infectious or allergic origin is an urgent task of both therapeutic and pediatric practice. This problem is of particular importance in connection with its prevalence in children, with a large list of drugs for the symptomatic treatment, the presence of significant side effects in active pharmaceutical ingredients, the peculiarities of the use of dosage forms, as well as a wide range of OTC drugs, including those approved for use in children.Aim. To develop recommendations for introducing changes or additions to the peculiarities of using decongestants for topical use in diseases of the nasal cavity (sympathomimetics, corticosteroids, antihistamines, etc.) in children (under 15 years of age) in the Protocol of the Pharmacist “Symptomatic treatment of rhinitis”.Materials and methods. To achieve the goal, the clinical and pharmaceutical analysis of decongestants for local use in diseases of the nasal cavity (sympathomimetics, corticosteroids, antihistamines, etc.), registered and marketed inUkraine was performed.Results. As a result of the study it has been found that in February 2020 there are 146 decongestants for local use in diseases of the nasal cavity registered at the Ukrainian market. 87.7 % of the drugs are OTC and can be used by patients/patient representatives independently. 12.3 % of the drugs (18 items, mainly from the group of corticosteroids) are dispensed by prescription. The analysis of the composition of decongestants has been performed; it has been found that agents based on oxymetazoline (21.2 %) and xylometazoline and its combinations (39 %) prevail. When studying the prescribing information it has been found that 136 of 146 trade names can be used in the case of a cold in children under the age of15. In addition, depending on the age, the ranking of their active pharmaceutical ingredients (APIs) can be presented by the following sequence: sodium chloride (0.65 %), phenylephrine hydrochloride (0.125 %), oxymetazoline hydrochloride (0.01 %). Clinical and pharmacological evaluation of undesirable effects of APIs and the ways of their prevention have been performed.Conclusions. The range and presence of undesirable effects of APIs of modern decongestants requires a cautious approach to responsible self-medication and a careful selection of the drug for the symptomatic treatment of acute rhinosinusitis in children. It is recommended to clarify the Protocol of the Pharmacist “Symptomatic treatment of rhinitis” on the possibility of using decongestants for topical use in diseases of the nasal cavity in children of different ages.
Today statins are considered as first-line drugs for treating dyslipidemia. Fibrates also have a place in the treatment of dyslipidemia. Taking the above into account it is relevant to highlight the evidence of the effectiveness of these drugs in reducing unfavorable outcomes of cardiovascular diseases (CVD) and feasibility of using them in the complex therapy of dyslipidemia, as well as the study of the pharmacoeconomic characteristics of fibrates presented at the Ukrainian pharmaceutical market. Aim. To analyze the clinical efficacy of fibrates in reducing the consequences of CVD, as well as to study the range, price characteristics, availability and consumption of fibrates at the Ukrainian pharmaceutical market from 2017 to 2019.Materials and methods. The analysis of the evidence of the clinical efficacy of fibrates in patients with CVD and dyslipidemia was performed in accordance to systematic reviews from the international Pubmed database. The retrospective analysis of the assortment, prices, affordability and consumption of fibrates in Ukraine was conducted according to the data from the “PharmXplorer” analytical system of the “Morion” information retrieval company and the Compendium system. The economic affordability was assessed by the value of adequacy of paying capacity (Ca.s.), the consumption volumes – by DDDs (the number of average daily doses) and the number of packages sold during 2017-2019.Results. The evidence of the clinical efficacy of fibrates in reducing cardiovascular events in patients with CVD and DM type 2 with dyslipidemia were summarized in systematic reviews. Within 2017-2019, only 3 trade names (TNs) of foreign fenofibrate, which prices did not fluctuate significantly, were registered at the Ukrainian pharmaceutical market. Fenofibrate drug – Lipofen NS (Nobel, Turkey), caps., 250 mg, blister No. 30, was highly available for the Ukrainian consumer (Ca.s. less than 5.0 %), and Traikor® (Abbot Products GmbH, Germany), film coated tablets, 145 mg, blister No. 20 and No. 30 (Ca.s. more than 5.0 %), were moderately available. The dynamics of the sales growth (2.4 times) of fenofibrate packages in 2019 compared to 2017 was determined due to the growth in sales of Traikor® (film coated tablets, 145 mg, blister No. 20). The dynamics of the increase in consumption of fibrates by the value of DDDs was found. It generally corresponded to the dynamics of sales in the number of packages, but the consumption volumes were insignificant.Conclusions. The use of fibrates in patients with CVD and dyslipidemia for the primary or secondary prevention of risks of adverse cardiovascular events leads to their decrease; moreover, in patients with DM type 2 it helps to reduce the risk of nonfatal myocardial infarction (MI) development. The consumption of fibrates at the Ukrainian pharmaceutical market is insignificant, and is determined by their clinical efficacy and the place in the antihyperlipidemic therapy of CVD where statins prevail today.
The modern pharmaceutical market offers a large number of drugs that promote the act of defecation. But at the same time medicinal plants should not be neglected in the treatment of constipation. Biologically active substances contained in them in their natural proportions may have a higher physiological effect with long-term use than their individual ingredients in patented drugs.Aim. To study the acute toxicity and the laxative effect of pectins isolated from Pimpinella anisum herb.Materials and methods. The acute toxicity of pectins isolated from Pimpinella anisum herb was determined in rats under conditions of a single intragastric injection. The laxative effect was studied in white rats compared to the drug “Senadex”. The percentage of increase in feces was determined as a criterion of the laxative effect.Results. After a single intragastric administration of the drug studied in the dose of 5000 mg/kg the death among animals was not observed. Pectins isolated from Pimpinella anisum herb in the test dose significantly increase the amount of fecal mass in animals by 88% compared to the control and are not inferior to the laxative effect of the reference drug “Senadex”.Conclusions. Pectin substances isolated from Pimpinella anisum herb are virtually non-toxic, have a pronounced laxative effect and can be used as a medicinal substance when creating drugs of this action.
Type 2 diabetes mellitus (DM2) has been increasing steadily all over the world. A large number of medicinal plants that have the hypoglycemic effect are known, but, unfortunately, currently there is very limited choice of antidiabetic herbal medicines.Aim. To design the experiment in order to study the hypoglycemic effect of polyphenolic extracts from bearberry (Arctostaphylos uva-ursi) leaves under the experimental insulin resistance (IR) in rats.Materials and methods. The experimental IR was induced by dexamethasone injections (Dex) and feeding with a high-fructose diet (HFD). Male outbred albino rats were randomized depending on the purpose of the experiment. As the study objects 50 % ethanolic polyphenol extracts obtained from bearberry leaves with addition of arginine (PE50_arg) and cysteine (PE50_cys) were selected. The oral glucose tolerance test (OGTT) was performed in all experimental groups of animals.Results. Dex had a more pronounced effect on tolerance to glucose compared to the HFD. It was shown that PE50_arg and PE50_cys after two weeks of administration revealed the ability to decrease the blood glucose level in rats, as well as reduce IR development and improve tolerance to glucose under the experimental IR. The hypoglycemic activity found did not much differ from the action of Metformin, but exceeded the activity of Arphazetin. These results can be the evidence of activation of glucose utilization processes, and it, in turn, indicates the insulin sensitivity improvement due to the action of the extracts studied. The data obtained indicate that the corrective effect of arginine and cysteine on signal transduction processes in insulin target cells plays an important role in the IR treatment.Conclusions. Bearberry leaves are the promising raw material for creating an anti-diabetic drug. Thus, it is necessary to further study the mechanisms of regulation of metabolic disorders when introducing new polyphenolic extracts.
The choice of an optimal drug is only one of the components of high-quality pharmacotherapy of acute rhinosinusitis, which is supplemented by providing a patient with full information about the action of the drug selected, its rational use and duration of drug administration, possible side effects, as well as drug and food interactions. There are no “good” or “bad” medicines because even the most effective drug can prove to be ineffective precisely through the wrong choice and insufficient information about its use. The solution to this problem will allow increasing not only the effectiveness, but also the safety of acute rhinosinusitis treatment. Today, phytoneering drugs occupy an important place in the treatment of patients with acute rhinosinusitis and have evidence-based effectiveness and safety. Thus, according to the EPOS 2020 recommendations, some herbal medicines are included into the treatment regimens for acute viral and post-viral rhinosinusitis with the level of evidence 1b by the GRADE methodology. A special place is occupied by the Sinupret products line manufactured by “BIONORIKA СE” company, Germany. All Sinupret drugs are related to the original plant raw material, the qualitative composition of the active substances that determine their pharmacological activity. “Sinupret®” contains standardized extracts of 5 plants: elder flowers (Sambucus nigra), primrose flowers (Primula versis), sorrel herb (Rumex acetosa), verbena herb (Verbena officinalis) and gentian root (Gentiana lutea). The high efficiency of each of the plants was confirmed by practical experience, and the therapeutic combination subsequently received a strong scientific basis. Due to the unique combination of biologically active substances of 5 medicinal plants “Sinupret®” exerts a versatile complex effect, breaking the “vicious circle” in rhinosinusitis. The pharmacodynamics of “Sinupret®” includes the following main effects: secretolytic and secretomotor, anti-inflammatory, anti-infective and immunomodulative. The administration of “Sinupret®” (taking into account the available pharmacodynamic effects) allows avoiding potentially problematic polypragmasia – simultaneous indication (in this context – unjustified) of several medicines to a patient, often for the treatment of the same symptom. This is especially true for the uncontrolled use of antibiotics without indications, and it has already led to the spread of such a dangerous phenomenon as antibiotic resistance all over the world.Conclusions. Considering the weighty data of evidence-based medicine the “Sinupret®” line medicines is an alternative choice for the treatment of persons with non-complicated acute rhinosinusitis.
Ultraviolet (UV) radiation, which almost the entire population of the planet is exposed to, is an etiopathogenetic factor in many diseases, including photodermatitis, sunburn, photoaging, carcinogenesis, photoallergy, etc. The use of photoprotective drugs and cosmetic products, which active pharmaceutical ingredients (AFIs) absorb or repel UV rays, helps to reduce the negative impact of sunlight on the body.Therefore, it is advisable to search and study new photoprotectors that can not only absorb or reflect the UV rays of a particular area of the spectrum, but also able to protect against broad-spectrum radiation.Аim. To study the photoprotective activity (PPA) of a new cream based on the composition of Salix alba L. bark and zinc pyrithionate conditionally named “Salizink” on the model of acute photodynamic inflammation of the skin in rats. “Psoricap” cream was chosen as a reference drug.Materials and methods. The photoprotective activity of “Salizink” cream was studied on the model of photodynamic injury caused by UV irradiation in rats.Results. The study has found that photodynamic inflammation of the skin developed gradually. On the background of the treatment with “Salizink” cream a significant decrease in the intensity of photodynamic inflammation of the skin of animals characterized by reduction of edema and hyperemia, as well as a decrease in the skinfold thickness were observed compared to the control pathology group (CPConclusions. The results of the study indicate that “Salizink” cream on the model of photodynamic UV-induced skin injury has shown marked anti-inflammatory properties. Its use has reduced the intensity of acute photodynamic inflammation and accelerated the recovery of experimental animals. The results obtained substantiate the feasibility of further study of “Salizink” cream as a photoprotective agent for the treatment of contact allergic dermatitis.
Among women, one of the common localizations of malignant tumors is ovarian cancer (OC). Two genes have been identified, and their mutations lead to hereditary forms of breast and ovarian cancer – BRCA1 and BRCA2. Women with BRCA-associated OC respond better to targeted drugs and have better survival rates against specific treatments. Targeted drugs for the treatment of BRCA-mutated OC are specific inhibitors of enzymes of the group poly- (ADP-ribose) polymerase (PARP). Currently, the only PARP inhibitor registered in Ukraine is olaparib (Linparza® drug, AstraZeneca, United Kingdom).Aim. To assess the economic feasibility of the targeted olaparib therapy (Linparza® drug) for patients with BRCA mutated platinum-sensitive recurrent ovarian cancer (BRCA-MPS ROC) from the standpoint of the Ukrainian healthcare system.Materials and methods. Determination of treatment outcomes and associated costs was performed using Markov analytical modeling based on the results of a randomized multicenter, open-label phase II clinical trial D0810C0019-Study 19. The model time horizon is 15 years. Clinical efficacy and safety of olaparib and placebo (WW strategy) were compared as the supportive therapy for patients with BRCA-MPS ROC. Based on the results of Markov simulation the methods of “cost-effectiveness” and “cost-utility” were used. Years of the saved life (LYG) were used as a criterion of efficiency. The QALY index was used as a criterion of utility. The cost of direct medical expenses, which structure was determined in accordance with the current Protocol, was taken into account. The cost of medical treatment was determined according to the register of the Ministry of Health of Ukraine as of 7.08.2019. The cost of medical services was determined according to the available price lists. The cost of correction of side effects of the chemotherapy was also considered. Discounting was determined at the level of 5 % annually. The sensitivity analysis of the results was performed on the price and dose of olaparib and the observation horizon.Results. According to the simulation, the average life expectancy of patients with BRCA mutated platinum-sensitive recurrent ovarian cancer when using olaparib (Linparza® drug) as a supportive antitumor therapy is 4.8 LYG compared to 2.56 LYG in the WW strategy group. The olaparib supportive care strategy provides the patient with 3.61 years of quality of life compared to 1.87 years in the WW group. Thus, the use of olaparib provides the patient with an additional 2.24 years of life and 1.74 additional QALY. The total costs for the simulated period in the group of olaparib averaged 1893410.7 UAH, and in the WW group – 47466.9 UAH. The incremental coefficients of ICER (cost of 1 additional year of life) and ICUR (cost of 1 additional year of quality life) amounted to 824564,4 UAH, and 1063162.2 UAH, respectively.Conclusions. The pharmacoeconomic analysis based on Markov modeling and cost-effectiveness and cost-utility calculations has shown that olaparib (Linparza® drug) is highly effective in the treatment of BRCA-mutated platinum-sensitive recurrent ovarian cancer; it almost doubles the patients’ survival without recurrence. At the same time, olaparib is an expensive drug. The transition of half of the patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer from the “watch-and-wait” strategy to the treatment with olaparib requires an additional annual cost of 10,548,250.3 UAH.
Diuretics increase the urine volume and sodium excretion, and therefore, they are often used to remove the excess fluid from the body during various diseases, including hypertension, heart and kidney failure, nephrotic syndrome, cirrhosis, and a number of other diseases.Aim. To study the diuretic activity of new benzyl acid derivatives.Materials and methods. The diuretic activity of the test compounds and the reference drugs – hypothiazide and furosemide was studied in intact white rats weighing 200.0 ±20.0 g by the method of Ye. B. Berkhin. Benzyl acid derivatives in the doses of 12 mg/kg and the reference drugs – hypothiazide and furosemide in the doses of 50 mg/kg and 20 mg/kg, respectively, were administered orally as aqueous solutions 60 min before the start of the experiment. A spontaneous diuretic activity was assessed by the amount of urine excreted in 2, 4 and 6 hours after the start of the experiment.Results. In the course of the study it was found that the diuretic activity was shown by substances KMS-68, KMS-70 and KMS-229 in 2 hours from the beginning of the experiment. The most active was KMS-229 (5-oxo-6,6-diphenyl-5,6-dihydro-4-H-benzo[d]thieno[3,4-b]azepine-3-carboxylic acid methyl ester), which significantly increased the volume of urine excreted compared to the control and the activity of hypothiazide by 2 times.Conclusions. The study of the diuretic activity of new derivatives of benzyl acid has been conducted. Compounds KMS-229 and KMS-70 have been shown to act as short-acting diuretics.
Today, according to the WHO, every fifth inhabitant of the Earth is infected with fungi, and every tenth has pronounced clinical manifestations of fungal diseases. The incidence of mycotic foot infections among the population both in Ukraine and in various European countries varies from 20 to 70 %.Aim. To analyze the assortment of antifungal drugs for systemic use at the pharmaceutical market of Ukraine within 2016-2018 and the evidence base for efficacy and safety of the antifungal drug – fluconazole.Materials and methods. The analysis of the assortment of antifungal drugs was performed within 2016-2018 according to the “Pharmstandard” information and search system “Morion” of company. The analysis of clinical efficacy and safety of fluconazole was carried out according to the evidence-based medicine databases, such as Cochrane Library, Trip Database, PubMed, Nice.Results. Antifungal drugs for systemic use were presented at the pharmaceutical market within 2016-2018 in a sufficient assortment (103-111 TN drugs) based on 7 INN. However, most INN drugs were presented by 1-4 TN and had a narrow price range per package. Only fluconazole preparations had a significant amount of TH at the market (79-89 TN drugs) with a wide range of prices per package (from 8.63 to 1407.29 UAH). In 10 systematic reviews analyzed the results of clinical efficacy and safety of fluconazole for the prevention and treatment of fungal infections in children and adults were presented. Fluconazole has the proven pronounced clinical efficacy and is recommended by the American and European Communities of Infectious Diseases as a first-line therapy for candida infections.Conclusions. The analysis of systematic reviews and meta-analyses prove the safety and efficacy of fluconazole when used in children and adults for the prevention and treatment of fungal infections.
Treatment of periodontal disease is one of the most important and complex problems of dentistry. Among periodontal diseases, gingivitis is the most common form of damage to the periodontal tissues; without proper treatment it tends to develop into a progressive form of periodontitis. Despite many years of experience in the use of stable combinations of antibacterial agents in dental gels, the creation of new combined drugs with the improved biopharmaceutical properties remains an urgent task for pharmaceutical industry.Aim. To study the wound-healing effect of the gel and determine the effect of the presence of hyaluronic acid in the composition on the intensity of the reparative process.Materials and methods. The wound-healing activity of new objects was studied on the model of a full-layer stencil wound. The test drugs were applied daily once a day in the dose of 20 mg/cm2 until complete healing. The main indicators of verification of the wound-healing effect of drugs were the area of stencil wounds, the rate of the healing rate and the percentage of animals with healed wounds.Results. The results of the dynamics of planimetric parameters showed that from the 4th and 7th days of the treatment the reduction of the wound area under the effect of the gel with hyaluronic acid was probably more effective than in the groups where the gel without hyaluronate and the reference drug were used. Complete epithelialization of wounds in all animals in the group where the combined gel was used was observed on day 14 compared to day 21 in the control group.Conclusions. By its reparative action the dental gel with hyaluronic acid is not inferior to the reference drug with methyluracil and miramistin and significantly exceeds the effectiveness of the gel without hyaluronate, which makes it a promising object for the in-depth pharmacological study and further clinical application.
Nonspecific (aerobic) vaginitis is a non-transmissible vaginal disease that occurs in a wide age range. Its prevalence ranges from 8 to 11% in pregnant women and from 5 to 24% in women who complain to a gynecologist. In this regard, the question of improving the therapy of vaginitis becomes especially relevant.Aim. To study biochemical changes in the venous blood on the background of the experimental vaginitis in rats in conditions of the treatment with suppositories “Melanizol” and “Klimedeks”.Materials and methods. The effect of the drugs was studied on the model of the experimental vaginitis caused by a single intravaginal irritant application in non-linear female rats.Results. It was found that on the background of the experimental nonspecific vaginitis in the group of untreated animals there was a significant increase in the level of total protein and the level of alanine aminotransferase in the serum. It indicates the presence of an inflammatory reaction in the body of rats. The urea levels tended to increase, but these changes were not significant. When studying the indicators of alkaline phosphatase and lactate dehydrogenase in the blood of animals no significant differences were observed among the groups studied. The suppositories “Melanizol” and “Klimedeks” under research significantly reduced the level of total protein compared to the group of untreated animals, and also restored the levels of the altered urea and alanine aminotransferase without inferiority to the effectiveness of the reference drug “Micogynaks”, and reliably exceeded the effect of the reference drug “Gravagin” by this indicator.Conclusions. Vaginal suppositories “Melanizol” and “Klimedeks” have shown an expressed anti-inflammatory activity on the background of the experimental vaginitis and are promising drugs for the treatment of nonspecific vaginitis.
Being a metabolic disease with long-term hyperglycemia, diabetes mellitus significantly increases the risk of microvascular and macrovascular diseases and organ pathologies, respectively. The creation of the new composition “Thigliben”, which allows not only qualitatively controlling diabetic hyperglycemia, but also providing a preventive and/or therapeutic effect on the development of diabetic polyneuropathy was pathogenetically reasonable.Aim. To study the antidiabetic activity of “Thigliben” on the experimental dexamethasone diabetes mellitus in rats.Materials and methods. The pharmacological study of the antidiabetic activity of the new composition “Thigliben” in the dose of 4 mg/kg was performed. The experimental studies were conducted on a standard model of the experimental dexamethasone type 2 diabetes mellitus in rats. Glibenclamide in the dose of 0.6 mg/kg (corresponds to an average human daily dose of 10 mg) was selected as the reference drug.Results. It was found that by its effects on the carbohydrate and lipid metabolism the new composition “Thigliben” was similar to the reference drug glibenclamide administered in a higher dose. By the antioxidant activity this composition exceeded the effect of the reference drug, provided that normalization of the TBA-RS level in the liver homogenate was significant. The new composition “Thigliben” normalized all the parameters of the cerebral energy metabolism studied relative to the control pathology group and its efficiency was significantly higher than that of the reference drug glibenclamide. The new composition “Thigliben” increased the content of ATP by 109 % compared to the control pathology group, in contrast to 68 % on the background of glibenclamide; restored the activity of citrate synthase by 65 %, succinate dehydrogenase by 134 %, and pyruvate dehydrogenase by 61 % relative to the control pathology group. For glibenclamide the change in these indicators was 28 %, 50 %, and 22 %, respectively. The results obtained suggest that the metabolic effect of “Thigliben” composition is significantly more effective than that of the reference drug glibenclamide.Conclusions. The new composition “Thigliben” is a promising antidiabetic drug with a pronounced hypolipidemic, antioxidant effect and the ability to restore energy deficiency; it is its significant advantage over the standard treatment regimens, including the average therapeutic doses of glibenclamide.
Diabetes mellitus is an important social and medical problem, as it causes the development of dangerous complications that lead to disability and mortality. This disease is characterized by a multi-vector pathogenesis that requires a comprehensive approach to treatment. Due to the using of medicinal plantsmixtures in the treatment of diabetes, it is possible to cover many aspects of the development of this disease and its complications.The aim of the study was to evaluate the hypoglycemic activity of some herbal mixtures and to establish their conditionally therapeutic doses on normoglycemic rats by glucose load tests.The study was performed on male albino rats weighing 180–200 g, which for preventive treatment during 20 days orally received aqueous extracts (1:10) of the studied herbal mixtures at a dose 6 mL/kg/day, 9 mL/kg/day and 12 mL/kg/day and comparison drugs – the official herbal mixtures «Arfazetin» at adose 9 mL/kg/day and metformin tablets at a dose 60 mg/kg/day. The study of hypoglycemic properties and the establishment of a conditional therapeutic doses was carried out using glucose loading tests (OGTT and IPGTT). All experiments were performed in accordance with general ethical principles and therecommendations of the EEC Council directive 2010/63/EU about the protection of animals, which are used for scientific purposes.The results of the study showed that the 20-day preventive administration of the herbal mixtures reduced alimentary hyperglycemia at the 30th min of OGTT and helped regulate carbohydrate tolerance disorders by reducing hyperglycemia at the 15th min of IPGTT. The highest hypoglycemic activity showedthe herbal mixture № 19 (Urticae folia, Taraxaci radice, Myrtilli folia, Rosae fructus and Menthae folia) at a dose 12 mL/kg/day, which was almost on a par with the comparison drug – metformin tablets, but exceeded the official herbal mixture «Arfazetin». In addition, the dose-dependence of the effectiveness of all five studied herbal mixtures was established.
