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The purpose of the research is to study the effects of ivermectin-containing drug in recommended and increased doses on adult dogs and cats.Materials and methods. The drug tolerance on dogs and cats was studied on 24 clinically healthy animals that were divided into experimental groups of 6 animals each, according to the principle of analogs, at the Podolsk Experimental Production Base of the VNIIP – FSC VIEV. The drug was administered seven times with a 3-day interval at a therapeutic dose of 0.2 mg of ivermectin per 1 kg of body weight to the first experimental group; and 0.6 mg of ivermectin per 1 kg of body weight to the second experimental group. The overall health status of the dogs and the cats was monitored daily, and blood samples were taken on days 20 and 34 of the experiment to study some morphological and biochemical parameters. Statistical data was processed in Microsoft Excel 2016 using the paired Student's t-test for dependent samples.Results and discussion. The studied ivermectin-containing drug had no negative effects on the adult dogs and cats’ overall health status, physiological status and behavior, or morphological and biochemical blood parameters. When using the drug in a threefold increased dose, three dogs and one cat showed depression which spontaneously disappeared within 48 hours. In addition, the animals from the second experimental group developed an allergic reaction, decreased functional activity of the liver and kidneys, and metabolic processes intensity, and red blood system destabilization. On day 34 of the experiment, the above changes were absent in the dogs and the cats, which indicates the restored physiological and biochemical status in the experimental animals.

Rosacea is a chronic inflammatory dermatosis predominantly damage to the skin of the face, which has a significant negative impact on the quality patients’ lives. The main goal of treatment is to achieve the most complete remission. However, due to the fact that the pathogenesis of the disease is not fully understood, the search for new methods of treatment is especially relevant. Combined use pulsed dye laser and ivermectin drug is presented as alternative pathogenetically substantiated method of therapy. The purpose of the study is to characterize immune disorders and the role of cytokines in the pathogenesis of rosacea, as well as the possibilities of combination therapy based on literature data. An analysis of literature sources from the MedLine, Pubmed, eLibrary databases for the period from 2002 to 2022 was carried out, using the keywords “ivermectin”, “pulsed dye laser”, “rosacea”, “cytokines”, “ivermectin” , “Pulsed Dye Laser”, “rosacea”, “cytokines”.

The purpose of the research is to detect long-term effects of repeated oral administration of supramolecular complex of ivermectin Aniverm-2.0% on the postnatal development of rat offspring.Materials and methods. The studies were conducted on 16 white pregnant rats that were divided into two experimental and one control groups. The animals were kept under standard conditions of keeping and feeding. The supramolecular complex of ivermectin Aniverm-2.0% was administered to pregnant female rats (n = 6) of group 1 in the form of a suspension using an intragastric tube daily for 7 days at a dose of 15 mg/kg, and group 2 was given the substance of ivermectin (n = 5) at a dose of 8.25 mg/kg. The control female rats (n = 5) were administered 1 mL of distilled water during the experiment. The experimental pregnant females were left until delivery, and then, the development of their offspring was monitored for 45 days. After rat pups were born, the following were recorded: pregnancy duration, litter size, dynamics of weight gain in the rat pups for 21 days, postnatal death during the first 30 days, the ratio of males and females in the litter, periods of eye opening, incisor eruption, detachment of the auricle, appearance of hair coat, descent of testicles, and opening of the vagina. Then we assessed the maturation rate of sensory-motor reflexes in the offspring obtained from the experimental and control groups, the emotional motor behavior and ability for fine coordination of movements in the offspring, and conducted the open field-2 test on day 45 after birth.Results and discussion. No negative effect was detected for supramolecular complex of ivermectin Aniverm-2.0% on the parameters of physiological development of the offspring of the experimental rats within 45 days after birth. The dynamics of their mass, developmental parameters, and formation of motor reflexes during the feeding period remained within the normal values. Developmental indicators of sensory motor reflexes in the control and experimental rat pups had no statistically significant differences.

The purpose of the research is to develop a methodology for Equiverm-2.0% paste used against equine parasite infections.The methodology provides a brief description of Equiverm-2.0%, mechanism of its action, pharmaco-toxicological properties, application, slaughter terms, and personal safety measures. Equiverm-2.0% antiparasitic paste consists of the active ingredient, ivermectin, and excipients; it is a light cream-coloured paste with a slight pine odor and sweetish taste. The drug is administered orally at a therapeutic dose of 0.2 mg/kg for the active substance. One gram of paste is equal to 1 mL in volume with 20 mg of ivermectin. Ivermectin in Equiverm-2.0% paste is in a dissolved form, and forms an intermolecular complex. The antiparasitic paste is packaged in disposable polyethylene syringe dispensers of 5 or 10 mL, respectively, 4 to 8 g each, per treated horse weighing 400-800 kg. When administered orally, the paste spreads in the oral cavity and the animal eats it with pleasure due to its sweetish taste. The drug is recommended for registration in the Russian Federation.

The purpose of the research is to evaluate the anthelmintic efficacy against gastrointestinal Strongylata infections of cattle and to give an economic justification for their use in Yaroslavl calves.Materials and methods. The studies were performed on the Ivanovo Region farms in 2018–2020. To determine the helminth infection in cattle, 604 animals undergone a coprological survey. The faeces were examined by the Fülleborn and Berman- Orlov methods. To determine the therapeutic efficacy of anthelmintics, 4 groups of animals spontaneously infected with Nematodirus sp. were formed. The first group of calves was dewormed with a drug containing 20% albendazole. The second group of animals received a drug containing eprinomectin, and the third, a combined anthelmintic containing praziquantel and ivermectin. The fourth group of calves was dewormed with an ivermectin containing drug. Results and discussion. On the Ivanovo Region farms, nematodirosis was recorded in the calves aged 6–12 months; the infection prevalence was 75.3% with an average intensity of 31.04±0.77 egg specimens in 1 g of faeces. The diets for calves on all of the farms were approximately the same; the average daily weight gain of the calves was 251.10±0.54 g. Drugs with the active substance of 20 % albendazole, eprinomectin, praziquantel + ivermectin, and ivermectin showed 100% extenseeffectiveness and intense-effectiveness. The release of the calves from Nematodirus spp. allowed to increase the average daily gain in the body weight of the Yaroslavl calves to 650±0.40 g. The applied anthelmintics showed an economic efficacy of RUB 12.7-13.1 for RUB 1 of costs.

The purpose of the research is to study the elimination period of Ivermectin residuals after three oral administrations of Iverbutan to broiler chickens.Materials and methods. For the experiment, 18 broiler chickens aged 28 days were selected. The birds were kept in the conditions of the Podolsk Experimental Production Department of the VNIIP – FSC VIEV. Iverbutan contains 0.4% of ivermectin and 10.0% of butaphosphan as active substances. The drug was administered orally by the group method at the rate of 1.0 mL of Iverbutan per 1 Liter of drinking water. Iverbutan was given three times: twice with a 24-hour interval and once after 14 days. The birds were killed and samples of their organs and tissues were taken at 9, 14, and 19 days after the drug was administered three times. Organs and tissues of each following type were collected from 6 birds: muscles, liver, kidneys, and skin with subcutaneous adipose tissue. The technique was based on the determination of Ivermectin by high performance liquid chromatography with modified pre-column accomplished with N-methylimidazole and trifluoroacetic anhydride, followed by fluorescence detection. The quantification was performed by the internal standardization.Results and discussion. The period was studied for elimination of Ivermectin residuals from the chickens’ body after the drug was administered three times. The residuals that exceed the maximum allowable levels were determined at 9 and 14 days after the drug was completed. It was found that the chickens’ organs and tissues did not contain Ivermectin at 19 days. Thus, poultry meat can be used for food at 19 days after Iverbutan is administered three times.

The purpose of the research is to study the effect of the new antiparasitic 2.0% Equiverm in high doses on the clinical state of horses.Materials and methods. The experiment was conducted on 15 two-year-old crossbred horses weighing up to 300 kg spontaneously infected with Strongylata. To determine the effect of the antiparasitic paste on the horses, three groups of five horses each were formed. The first group of the horses was administered 2.0% Equiverm at a therapeutic dose; the second, at a three-fold increased dose, and the third, at a five-fold increased dose (0.2; 0.6 and 1.0 mg/kg for the active substance (AS), and 1.0; 3.0 and 5.0 mL per 100 kg of body weight for the drug). The horses’ clinical state was studied using standard methods. Blood samples for the study were taken from the jugular vein before the drug on the first, third and seventh days. The results obtained were statistically processed using the computer tool Microsoft Excel 2007.Results and discussion. It was found that the antiparasitic paste 2.0% Equiverm had no negative effect on clinical, hematological or biochemical parameters after a single oral administration at a therapeutic, three- and five-fold increased dose (0.2; 0.6 and 1.0 mg/kg for the AS, and 1.0; 3.0 and 5.0 mL per 100 kg of the body weight for the drug).

The purpose of the research is to study effects of the 2.0% supramolecular complex of ivermectin in overdoses on the clinical condition of horses.Materials and methods. The experiment was conducted on 20 horses of different breeds in the Seradin Equestrian Center, the North Caucasus Federal District, the Chechen Republic, in October 2020. The horses were divided according to the principle of analogues into 3 test groups and one control group of 5 animals each. The 2.0% supramolecular complex of ivermectin was administered to the horses from group 1 at a therapeutic dose of 0.2 mg/kg; group 2 received a tripled dose of 0.6 mg/kg, and the group 3, a 5-fold increased dose of 1,0 mg/kg for the active substance. The drug was administered once individually in a mixture with compound feed. The body temperature was measured with a non-contact thermometer, and the pulse rate and the respiratory rate were measured per 1 min. Urine of the horses was examined on days 1, 7 and 14 after the drug. The urine color, transparency and consistency were determined. Multifunctional test paper was used to study pH, protein, glucose, ketone bodies, nitrites, bilirubin, and urobilinogen. Blood was taken in the morning from the horses’ jugular vein on days 1, 7 and 14 after the drug. Hematological and biochemical parameters were studied on analyzers.Results and discussion. Clinical fndings of the horses (body temperature, pulse and respiration) did not differ from those of the control animals after the 2.0% supramolecular complex of ivermectin was administered in a therapeutic, tripled and 5-fold increased doses on days 1, 7 and 14. A slight increase in ketone bodies was observed in the urine on day 1, which may indicate the drug effect on the central nervous system at a 5-fold increased dose; all parameters were within the normal range on days 7 and 14. The 2.0% supramolecular complex of ivermectin in overdoses (0.6; 1.0 mg/kg for the active substance) did not adversely affect the horses’ hematological or biochemical blood parameters.

Introduction. Ivermectin is an antiparasitic drug that has been widely used in veterinary medicine. Parasitic diseases of farm animals cause great economic damage and pose the risk of human infection. Prolonged dosage forms of ivermectin are effective against them. The first step in the creation of such a drug was the preparation and study of polymeric microparticles of polycaprolactone with encapsulated ivermectin.Aim. Obtaining polymeric microparticles of polycaprolactone with encapsulated ivermectin using a continuous flow-through unit.Materials and methods. The object of the study was microparticles of polycaprolactone with encapsulated ivermectin obtained on a continuous flow-through unit. Determination of the average particle size and size distribution was carried out by the method of laser diffraction. Microscopy was used to visually assess the shape and size of the microparticles. UV – spectrophotometry was use to quantitative determination of ivermectin.Results and discussion. Polymeric microparticles of polycaprolactone with encapsulated ivermectin was obtained and had an average size of 126.63 ± 42.67 μm and contained 32,73–62,00 % of ivermectin. Suspensions prepared from the obtained microparticles were passed through a 20G injection needle without noticeable resistance, which indicates the possibility of their use as the basis of an injectable preparation.Conclusion. Obtained results confirm the possibility of using flow-through dispersion using a device developed by us for obtaining polycaprolactone microparticles with encapsulated ivermectin, which are suitable for injection. Thus, the results obtained make it possible to continue studies of microparticles and create a drug based on them.

The search for an effective and safe COVID-19 therapy involves, among other things, assessment of efficacy of medicines already used for the treatment of other diseases, and having potential antiviral activity against SARS-CoV-2. The relevance of the presented study stems from ambiguous data on the off-label use of the antiparasitic medicine ivermectin for the treatment of COVID-19 patients. The aim of the study was to analyse ivermectin efficacy and safety for COVID-19 treatment, as reflected in the scientific literature. Ivermectin, an antiparasitic medicine from the group of macrocyclic lactones produced by Streptomyces avermitilis, stimulates release of the inhibitory neurotransmitter gamma-aminobutyric acid, which leads to impaired transmission of nerve impulses, paralysis and death of parasites. The results of preclinical studies show ivermectin’s inhibitory activity against a number of RNA and DNA viruses, including SARS-CoV-2. The results of ivermectin clinical studies are ambiguous: a number of studies demonstrated a positive effect on the condition of COVID-19 patients, however, there is currently no convincing evidence of the validity and efficacy of ivermectin use for the prevention and treatment of COVID-19 patients. The safety profile of ivermectin is relatively favourable. Large randomised controlled trials are needed to fully assess the feasibility of using ivermectin in COVID-19.

Introduction. Ivermectin is known as a veterinary agent with a wide spectrum of action against endo-and exoparasites of farm animals, which makes its use promising. Therefore, the possibility of creating prolonged parenteral dosage forms using polymer biodegradable carriers is currently being investigated. To carry out their quality control, a method of quantitative determination of the active substance is necessary. Most of the previously proposed methods are characterized by time-consuming sample preparation, complex composition of the mobile phase or a long analysis time, therefore, during the development of an injectable prolonged preparation of ivermectin based on polycaprolactone microparticles, a new method for the quantitative determination of ivermectin was proposed, which is simple and suitable for use in production.Aim. Development of a method for the quantitative determination of ivermectin in the composition of polycaprolactone microparticles and its validation.Materials and methods. Microparticles with ivermectin were used as the object of the study. The method of quantitative determination of ivermectin in the test sample was developed on a high-performance liquid chromatograph Dionex UltiMate 3000 (Thermo Fisher Scientific, USA), equipped with a diode-matrix detector.Results and discussion. In this paper, various conditions for the quantitative determination of ivermectin in the composition of polymer microparticles are studied. Based on the obtained data and results, a method has been developed that has optimal sample preparation and analysis conditions.Conclusion. As a result of the development, the conditions for the analysis were selected, which allow us to evaluate the quantitative content of ivermectin in the sample. The method was validated for the parameters specificity, analytical area, linearity, trueness, repeatability, intermediate precision.

The purpose of the research is to study the acute oral toxicity of the medicinal product for veterinary use Iverbutan, intended for the treatment and prevention of arachnoentomoses and nematodoses of poultry.Materials and methods. The studies were carried out on 30 outbred male rats weighing 210-240 g and 60 mice weighing 18–21 g. The animals were divided into experimental and control groups. The drug was administered once without dilution in the form of the provided solution using an intragastric tube. Doses of 2000, 4000, 6000, 8000 and 10 000 mg/kg were tested on mice, and on rats – 10 000, 8000, 5000, 4000 mg/kg. The animals of the control groups were injected with drinking water. Within 14 days after a single dose of the drug, the physiological state and behavior of animals, possible death, as well as the manifestation of symptoms of intoxication were monitored. The control of the body weight of the animals of the experimental and control groups was carried out on the day of the experiment (before drug administration), as well as on the 1st, 3rd, 7th, 9th and 14th days.Results and discussion. It was found that after oral administration of iverbutan to experimental animals, the average lethal dose, calculated by the Kerber method, was 5600 mg/kg of body weight in mice and 7000 mg/kg of body weight in rats (hazard class 4 according to GOST 12.1.007-76). The average lethal dose, calculated by the Miller and Tainter method, was 5292.0±1058.6 (4233.4÷6350.6) mg/kg of body weight in mice and 6463.2±1496.9 (4966.3÷7960.1) mg/kg of body weight of rats (hazard class 3 according to GOST 12.1.007-76), which indicates species sensitivity.

The purpose of the research is a commission test of the efficacy of the supramolecular complex of ivermectin at gastrointestinal strongylatoses of horses.Materials and methods. The commission experiment was performed in June 2019 in the North Caucasian Federal District of the Chechen Republic. The efficacy of the supramolecular complex of ivermectin was evaluated on 20 horses of different breeds in the Seradin Equestrian Center. To determine the rate of gastrointestinal nematode infection in horses, we collected fresh feces in the morning, made tissue imprints from perianal folds and examined them by the Fülleborn's method using a saturated solution of sodium chloride.Results and discussion. The coproovoscopic examination determined a 100% infection of horses with Strongylates and 40.0% infection with Oxyuris sp., with 488.7±24.4 strongylates eggs and 16.9±0.84 Oxyuris sp. eggs found in 1 g of feces, respectively. Seven and 15 days after the supramolecular complex of ivermectin administered to the horses from the first test group at a dose of 0.15 mg/kg for the active substance (7.5 mg/kg for the drug) in a mixture with mixed feed, we did not find any Strongylata eggs or Oxyuris sp. eggs in feces or on tissue imprints. Insufficient efficacy was obtained in the horses from the second test group after being treated with the active substance of ivermectin at a dose of 0.15 mg/kg. The strongylate egg number decreased on average by 244.3±12.21, namely, by 50.1%, and no Oxyuris sp. eggs were found. The efficacy against Oxyuris sp. was 100%. The horses consumed the mixture of drugs with feed readily. There were no side effects after the drugs applied. Thus, we established the high efficacy of the supramolecular complex of ivermectin against gastrointestinal strongylatoses, and the convenience of its use in a mixture with feed to untamed herd horses individually and by group feeding.

The purpose was to study therapeutic properties of Lipomek 2% drug in animals affected with siphunculatosis, and to determine duration of its action against this pathology. To achieve these goals, 2 species of animals were used. Experiments were conducted at 2 different farms - Mygra and Fazenda, where 25 sheep (Lezgin breed) and 17 calves (Caucasian brown breed) were studied. Animal siphunculatoses are the most common parasitic diseases in Rutul village (Rutul district, Republic of Dagestan). The effectiveness of a new long-acting antiparasitic drug Lipomek 2% (ivermectin) against siphunculatosis in small and bovine animals was studied. A 1% solution of ivermectin also showed a good therapeutic effect which was manifested next week after injection and lasted 21 days. Lipomek 2% (ivermectin) showed 100% efficacy against siphunculatosis in sheep and calves. Duration of parasitocidal effect was maintained for up to 30 days (observation period). No signs of intoxication were observed after livestock treatment.

High priority of soil-transmitted helminths worldwide and in the Russian Federation is due to their vast distribution and the severe pathological features they induce in humans. Recently, it was observed that awareness of clinicians regarding this disease category was markedly decreased, although no significant decline of the disease occurrence has been recorded, whereas rate of imported cases of parasitic diseases including soil-transmitted helminths like strongyloidiasis mainly originating from subtropical or tropical countries rose in non-endemic regions. Lack of alertness on diseases like strongyloidiasis impedes timely diagnostics and treatment. Global prevalence of strongyloidiasis was estimated to range within 30—100 million people, however the World Health Organization (WHO) suggests that it was underestimated as precise data in endemic countries remain unknown. The occurrence of these helminths has been recorded in regions of temperate-continental climate: Western Ukraine, Belarus, Moldova, the Caucasus, Central Asia, as well as in Eastern Europe and the Mediterranean region. In the Russian Federation locally acquired infections are frequently recorded in the Krasnodar Territory and Rostov Region. Here, based on multi-year experience in management of patients with strongyloidiasis we present our data and brief review of publications and systematic literature related to the challenges of its clinical picture, diagnostics and treatment. Life cycle, basic biological parameters of free-living helminth in nature and distinctive features of autoinfection related to strongyloidiasis were reviewed. Special attention was paid to the risk of developing severe forms (hyperinfection and disseminated strongyloidiasis) especially in immunocompromised hosts: HIV infection, radiotherapy followed by chemotherapy, long-term corticosteroid use. Difficulties in diagnosing Strongy-loides stercoralis infection are due to its polymorphic and non-specific clinical manifestations, as well as the lack of clinical knowledge and awareness about the disease. Clinical importance of parasitological methods for larvae detection was underlined. It was noted that the drug of choice in therapy of strongyloidiasis is ivermectin unapproved yet in Russia, whereas albendazole as an alternative drug exerts poorer efficacy, justifying a need to repeat treatment courses to establish full recovery from the disease.

The purpose of the research is to test the efficacy of the supramolecular complex of ivermectin against gastro-intestinal nematodes of herd horses under production conditions. Materials and methods. The test of the efficacy of the supramolecular complex of ivermectin was carried out from December 2018 to January 2019 in the North Caucasus Federal District of the Chechen Republic. Two herds of horses of 47 and 54 heads in each of different ages were selected, which were grazed all year round. To determine the infection of horses with nematodes of gastro-intestinal tract, 20 samples of fresh feces from each group were collected from the ground. It was not possible to collect samples from untamed horses to determine the infection by Oxiuris spp. Coproovoscopy was performed using the Fülleborn method. To count eggs in 1 g of faeces, a VIGIS counting chamber was used. The first group was given a 2.0% drug individually in a mixture with food at a dose of 0.15 mg/kg for active substance (AS) (according to the drug 75 mg). The drug was administered to the second group at a dose of 0.2 mg/kg for AS (for the drug 1.0 mg/kg) by the group method in a mixture with food, calculated on a live weight of 500 kg. The efficacy of the drug was determined 2 weeks after deworming according to coproovoscopy data. The efficacy of ivermectin complex was accounted for by the "critical test" method. After deworming, the animals were observed during the experiment. Results and discussion. Dehelminthization of horses with a supramolecular complex of ivermectin at a dose of 0.2 mg/kg for AS in a mixture with mixed feed by a group method for mixed infection of various types of gastro-intestinal nematodes under production conditions showed 100% efficiency. Arabinogalactan in the supramolecular complex helps to eliminate the negative effect of AS (ivermectin) on the animal body. The mixture of the preparation with the food was readily consumed by the horses. Deworming horses of herd keeping with a preparation intended for use in a mixture with feed is technically convenient, practically uncomplicated, and at the same time, physical exertion during fixation of animals and industrial injuries are excluded. We did not observe any side effects after deworming horses.

The purpose of the research is evaluating the efficacy of the antiparasitic complex based on ivermectin obtained by mechanochemical technology against gastrointestinal nematodosis of herd horses.Materials and methods. The efficacy of the ivermectin-based antiparasitic complex was tested in December-February 2019 in the Southern Federal District of the Chechen Republic in a private farm on 22 stabled foals aged over one year. To diagnose gastrointestinal parascaridosis and strongylatosis, feces of foals were examined using the Fulleborn’s method. Helminth eggs in 1 g of feces were counted in a counting chamber of the All-Russian Scientific Research Institute of Helminthology. In order to diagnose oxyurosis, pieces of transparent adhesive tape with prints from perianal folds were transferred to a glass slide and examined for Oxyuris spp. eggs. The antiparasitic complex of ivermectin 2% was administered in a mixture with food at a dose of 0.1 mg/kg by the drug (0.2 mg/kg by the active substance). After a preliminary test of the ivermectin complex efficacy, the therapeutic dose of the drug was titrated on 46 adult horses (aged 2–4 years) from the same private entrepreneur. The horses spontaneously infected with Strongylata, Parascarids and Oxyurises were divided into 5 groups according to the analogue principle. For animals of groups 1, 2, and 3, the drug was administered at a doses of 0.1, 0.15 and 0.2 mg/kg by the AS respectively. The horses of groups 4 and 5 were given the substance of ivermectin at a doses of 0.1 and 0.2 mg/kg by the AS, mixed with combined feed individually. The efficacy of the supramolecular complex of ivermectin was recorded according to the data of coproovoscopic studies using the critical test method according to the Guidelines approved by the World Association for the Advancement of Veterinary Parasitology (1995). Results and discussion. The rate of infection of the foals with Strongylata, Parascarids and Oxyurises was 100, 40 and 55% respectively as resulted from the coproovoscopic studies. The dissections showed that the intensity of infection with Strongylata was equal to 477.4±23.87 individuals per animal, Parascarids 447.1±55.89, and Oxyurises 22.2±2.02. The 100 % efficacy was determined for the antiparasitic complex of ivermectin at a dose of 0.1 mg/kg by the drug (0.2 mg/kg by the AS) against the main gastrointestinal nematodes. The substance of ivermectin at a dose of 0.2 mg/kg showed 87.5% efficacy against Strongylata and Parascarids, and at a dose of 0.1 mg/kg, it showed a lack of efficacy (50.0 and 25.0% respectively). We recognized the dose of 0.15 mg/kg by the AS of the supramolecular complex of ivermectin with one-time individual use in a mixture with food as therapeutic.

The purpose of the research is to study the cumulative properties of the supramolecular complex of ivermectin.Materials and methods. Studies were conducted in the vivarium of the VNIIGIS named after K. I. Skrjabin. For the purpose of the experiment, 20 outbred white rats weighing 180 g were selected, which were divided into experimental and control groups of 10 animals each. To determine the cumulation coefficient, we used a method taking into account the death of animals upon repeated administration of the drug — a test of subchronic toxicity in accordance with the “Guidelines for the experimental (preclinical) study of new pharmacological substances”. For the rats in the experimental group the drug was administered orally during the first four days at a dose of 35.5 mg/kg equal to 1/10 of the previously established single LD50 (298.0 mg/kg). Then, the dose was increased by 1.5 times every next four days. The rats in the control group were injected with 2 ml of water. The experiment was carried out for 28 days. Throughout the experiment, animals were monitored, considering their condition and degree of activity.Results and discussion. According to the accepted classification, the supramolecular complex of ivermectin belongs to the group of substances with weakly expressed cumulative properties, since the cumulation coefficient is 6.05 (IV toxicity group).

The purpose of the research: study of Ivermectin pharmacokinetics in horses organism after the application of Equiverm antiparasitic paste. Materials and methods. For studying of pharmacokinetics of Equiverm in blood plasma of five manorial breed horses at the age of 6-7 years, with the weight about 400-450 kg antiparasitic paste was injected orally by syringe dispenser in an amount of 0.2 mg/kg body weight, and then blood sampling from jugular vein was performed in 1, 2, 3, 5, 7 ,9, 24, 48, 96, 144, 288, 456, 624, 720 hours for the following determination of the concentration of Ivermectin in blood plasma of horses by high pressure liquid chromatography with ultra-violet detection using P.K. Sanyal method (1994). Validated method of determination Ivermectin in blood serum of was developed. It allows determining this analyte in extremely low concentrations (LOD value is 0.03 ng/mL, LOQ value is 0.09 ng/mL). Results and discussion. Ivermectin is absorbed in horses digestive tract after oral administration and it reaches defined blood serum concentrations in 1-2 hours after oral administration of antiparasitic paste - 0.2 ng/mL. Maximum concentration of 0.84 ng/mL was registered in 7 hours, and Ivermectin level decreased gradually to 0.2 ng/mL by the fourth day. Therefore, upon oral administration of Equiverm antiparasitic paste ivermectin was absorbed well enough and it enters the systemic circulation where it circulates during 4 days. Only trace amounts of Ivermectin are determined two weeks after drug administration.

The main pathogenetic aspects of rosacea, various classifications of dermatosis and the modern clinical classification are presented. The symptoms of different forms of rosacea are described. Contradictory of modern scientific concepts of different researchers, approaches to etiology, pathogenesis and treatment has been noted. The main triggers for the manifestation of rosacea, which should be tak en into account to achieve the maximum effect in the treatment of the disease, are indicated. The first domestic positive experience of authors with 1 % ivermectin cream and 0.03 % tacrolimus ointment is presented. The high efficacy and very good tolerability of this combination, compared to monotherapy of 1 % ivermectin cream and traditional therapy of metronidazole cream and azelaic acid gel as well as the absence of any side effects in patients with moderate to severe rosacea are shown.

Objective of research: To evaluate the tolerability of the drug, “Inspector Collar” based on Fipronil, Pyriproxyfen and Ivermectin in dogs and cats applied at a therapeutic dose and double increased therapeutic doses.Materials and methods: Research was conducted at the shelter for dogs and cats «Bano Eco» (Moscow). Effect of drug “Inspector Collar” was studied on 15 clinically healthy outbreed dogs between 2 and 6 years with the body mass of 10–14 kg and 15 clinically healthy outbreed cats between 2 and 4 years with the body mass of 2–3,5 kg, receiving complete and balanced nutrition. Animals were divided into six groups (three groups of dogs and three of cats) five animals in each group. Dogs and cats from the first experimental group had put on one collar (equivalent of single therapeutic dose) for 45 days. The second experimental group had put two collars (double therapeutic dose) for 45 days. Animals from the third (control) group did not carry collars. During the experiment, daily supervision of animals was conducted; their general health status, behavior, appetite were observed, body mass and temperature estimated. Before and 15 and 30 days after the beginning of drug application, blood and urine tests were performed to study morphological and biochemical parameters. Statistical processing of data were carried out using Student’s t-test.Results and discussion: The research results showed that the drug “Inspector Collar” is well tolerated even at double therapeutic dose. All observed indicators remained within the physiological norm.

The pharmacokinetics and dynamics of ivermectin removal from sheep organism is studied. Iverlong contains in sheep organism at level below a limit of detecting of the method.

Injection of ivermectin in a dose of 0,2 mg/kg to pregnant rates in critical stage of embryogenesis at days 1-6, 7-14 and 15-19 did not effect animals’ beha- vior. Duration of pregnancy in laboratory female rats was at control and normal physiological level for present kind of animas. Delivery process was normal with- out clinical features and complications. Presence of milk in rats’ stomachs allows to conclude that the injection of tested medicine to female rats did not affect their lactation and sucking reflex. At injection of ivermectin in a therapeutic dose at days 1-6, 7-14 and 15-19 of pregnancy the value of rats' death in the first life month was compatible with control values. According to our observation there was no effect of ivermectin on postnatal development in rats in form of death and external malformations. All rats were born healthy, responded well to external stimuli, had a good appetite and pursued an active life. Results of laboratory research allow to conclude that ivermectin injection to rats in a therapeutic dose of 0,2 mg/kg in dif- ferent pregnancy terms including critical stages doesn't have embryotoxic and tera- togenic effects

Adult Dermacentor marginatus hatched from nymphs infected with TBE virus and poisoned with ivermectin retain their vector abilities. Even small individuals with a 1.5-2 times lesser mass as against the reference mass contain the virus in the body in the same titers and the virions in salivary gland alveoli. Administration of an oil solution of ivermectin into the stomach of white mice, nymph feeders, in a dose surpassing threefold the dose recommended for intramuscular injection of this agent completely suppressed shedding of intact nymphs but did not suppress it in those infected. The nymph mass, size and mass of adult ticks hatched from them dropped under the effect of ivermectin dosage build-up in both intact and infected ticks, but these processes were slower in ticks infected with TBE virus. The authors suggest that the ticks infected with TBE virus are much more resistant to the process of gamma-aminobutyric acid depression, the mechanism of ivermectin action. They emphasize the necessity of bearing in mind the possible differences in the reactions to systemic poisons of intact and infected ticks when organizing vector control measures.

The effect of Ivomec, a formulation of ivermectin administered by various routes: through biological membrane and feeder animal was assessed. Higher insecticidal effect was obtained by feeding mosquitoes with blood containing ivermectin through biological membrane. Anopheles stephensi females were the most sensitive of 3 species under study. Their total death after feeding was observed at 1 ppm, while for Aedes aegypti the lethal dose was 2.5 ppm and for An. sacharovi, 50 ppm. Subcutaneous injection of the drug to rabbits at the dose 0.34 mg/kg wt with further feeding on it of 3 Anopheles species demonstrated the highest drug sensitivity of An. stephensi mosquitoes. Death rates among the females fed on the rabbit 4-6 days after injection of the drug were 93, 70 and 79%, respectively. Death rates among An. sacharovi and An. atroparvus differed only slightly from that of the control group. In some experiments ivermectin effect on female fertility and larvae hatching from ova can be traced. Probably, increasing the preparation dose, administered to an animal-feeder, may change significantly characteristics of the malaria carrier natural population. Moreover, further use of ivermectin versus helminths and mosquitoes in zootechnical practice may produce a side-effect on mosquitoes, feeding recurrently on domestic animals, thus increasing the effect of malaria zoological control.