Introduction. Insulin is the most effective hypoglycemic agent currently used in the clinical practice. Compared with recombinant human insulin, insulin lispro have a blood glucose profile that is much closer to physiological. The clinical trials program of insulin bioassays includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD), and a clinical safety study.Aim. To compare PK and PD of RinLiz® U100, solution for intravenous and subcutaneous administration (LLC «GEROFARM», Russia) and Humalog® U100, solution for intravenous and subcutaneous administration (Lilly France, France) in hyperinsulinemic euglycemic clamp.Materials and methods. This was randomized double-blind, two-arm crossover study in 28 healthy volunteers (NCT03604575). The studied preparations were injected before the clamp with a dose of 0.3 U/kg once subcutaneously in the area of subcutaneous fat in the anterior abdominal wall. During the study, regular blood sampling was performed; the amount of insulin lispro was determined by ELISA in the samples. The results of the determination were used to calculate the PK parameters and construct the curves «concentration – time». Based on the measurement of glycemia, the glucose infusion rate was adjusted. These data were used to calculate the PD parameters. The comparability of the studied drugs was considered proven if 90 % confidence intervals (CI) for the ratio of geometric mean PK parameters Cins. max and AUCins. 0-8 and 95 % CI for the ratio of geometric mean PD parameters GIRmax and AUCGIR0-8,5 were in the range of 80–125 %. Statistical data processing and presentation of the results was carried out using software packages R 3.4.2.Results and discussion. In the course of CI comparative PK and PD of RinLiz® and Humalog®, it was revealed that they have comparable PK and PD profiles. The CI for the logarithmically converted ratios of the values of the PK parameters was Cins. max 85.99–96.85 % and AUCins. 0-8 90.58–97.28 %, the PD of the parameters were 95.64–118.94 for GIRmax and 96.5–121.36 for AUCGIR0-8.5, all the CIs correspond to the set the boundaries of 80–125 % to establish comparability between RinLiz® and the original drug.Conclusion. The results demonstrated the high degree of similarity of RinLiz® U100 and Humalog® U100 in terms of PK, PD profiles and safety.

A study of the toxic properties of the drug cabazitaxel was carried out on outbred rats with intravenous administration. The toxicity was assessed with a single and repeated weekly administration of the drug. It was noted that the toxic and lethal effects were delayed. In an acute experiment, the mean lethal dose was calculated, which for animals of both sexes was 4.2 mg/kg. With repeated administration, the maximum tolerated dose was 1.5 mg/kg, lethal - 2.5 mg/kg. The clinical picture of intoxication was characterized by depressed behavior, decreased response to external stimuli and tonus of skeletal muscles, tachypnea and diarrhea. A decrease in feed intake and body weight of animals was detected. Target organs of toxic effect of cabazitaxel: gastrointestinal tract, liver, bone marrow, reproductive system of male rats.

A study of the toxic properties of the drug cabazitaxel was carried out on outbred rats with intravenous administration. The toxicity was assessed with a single and repeated weekly administration of the drug. It was noted that the toxic and lethal effects were delayed. In an acute experiment, the mean lethal dose was calculated, which for animals of both sexes was 4.2 mg/kg. With repeated administration, the maximum tolerated dose was 1.5 mg/kg, lethal - 2.5 mg/kg. The clinical picture of intoxication was characterized by depressed behavior, decreased response to external stimuli and tonus of skeletal muscles, tachypnea and diarrhea. A decrease in feed intake and body weight of animals was detected. Target organs of toxic effect of cabazitaxel: gastrointestinal tract, liver, bone marrow, reproductive system of male rats.

The article summarizes experimental data on toxicological interactions of blocker of amplodipine slow calcium channels with angiotensin II (AT1 subtype) receptors blockers (valsartan and losartan). Toxicity studies were performed in outbred rats after a single intragastric administration in doses permitting to estimate lethal doses for the objects under investigation (amlodipine, valsartan, losartan, amlodipine+ losartan 1:10, amlodipine+ losartan 1:20, amlodipine + valsartan 1:16, amlodipine + valsartan 1:32). Based on the research outcome, the possibility of different types of toxicological interaction is shown between representatives of classes of slow calcium channels blockers and angiotensin II receptors blockers: from potentiation of toxic effects to the antagonism in relation to toxicity. Identified toxicological interactions in fixed combinations depend on the proportion of active ingredients in the combination, as well as on modes of action features and pharmacokinetics of each active ingredient.

During this work it was studied the influence of the new entretenimiento of natural origin (DPP-4 inhibitor, the drug KLS-073) on basic biochemical parameters for a long period (12 months) of application. The experiment was carried out on outbred mice of both sexes. The introduction of the drug was carried out during 12 months in three doses: higher therapeutic (ITD) (2 mg/kg), 5 ITD (10 mg/kg) and 10 ITD (20 mg/kg). As of the evaluation criteria in the assessment we used overall biochemical and hematological parameters and histological examination of the thyroid and the pancreas over time (the 31st, the 91st, 181st and 361 th days). According to the results, the study showed no differences in biochemical parameters and structure of the thyroid and pancreas glands of intact animals and animals treated with the study drug KLS-073.

In article the data obtained experimentally on toxicity of representatives of various groups of inhibitors of system of RAAS are generalized: renin inhibitors (aliskiren), inhibitors of angiotenzintransformation enzyme (AAE) (enalapril, fosinopril), blockers angiotensin II (ATII) of receptors (valsartan, losartan, telmisartan, irbesartan). Researches of toxicity are conducted on the outbred rats at single and repeated (30 days) intragastric introduction in the doses equivalent of 1, 10 and 20 of highest to therapeutic for persons. By results of researches all studied representatives are carried to a class of low-toxic medicines. Toxic influence is revealed after repeated introduction of preparations in doses of 10 and 20 highest therapeutic. Main target organs of toxic influence: cardiovascular system, kidneys, liver is the minimal influenced.

In outbred rats a comparative toxicological evaluation of a nanoparticulate paclitaxel polylactide-based formulation, a liposomal docetaxel formulation and their standard drug formulations was conducted. Results of acute toxicity study revealed equivalent toxicity of standard and nanoscale formulations. Subchronic toxicity study showed a significant reduction in hematotoxicity, a decrease of cytotoxic effects on the thymus and the spleen for the nanoscale formulations.

Betulin is a pentacyclic triterpene alcohol belonging to the lupane series of compounds. It is extracted from the outer birch bark. The birch triterpenes have known antiallergic, antiviral, antimicrobial, antitumor and hepatoprotective effects [1–3]. Although to our knowledge no reports about acute toxicity of betulin were published. Acute toxicity of betulin was studied on rats and mice.