Preclinical studies of the effects of a drug based on ethylmethylhydroxypyridine succinate and a phosphodiesterase-3 inhibitor on laboratory animals

The study of a drug’s toxicity is one of the key stages in pharmaceutical development. Preclinical studies form the evidence base for the therapeutic efficacy and safety of a medicinal product. The data obtained in such studies allow for the prediction of long-term effects associated with the use of a new drug. The aim of the present study was to experimentally determine the parameters of acute and chronic toxicity of the drug Bendamin in laboratory animals, as well as to assess its cumulative properties.The determination of the acute toxicity of Bendamin revealed that, when administered intragastrically, the drug belongs to toxicity class IV, with an LD₅₀ value exceeding 5000 mg/kg. It does not exhibit cumulative effects, with a cumulation coefficient of 8.31 units. The study of chronic toxicity of Bendamin in white rats demonstrated that prolonged administration for 30 days, either in a therapeutic dose or in a fivefold dose, did not cause clinical signs of poisoning. This was confirmed by physiological fluctuations within normal limits in the studied hematological and biochemical parameters of the rats’ blood. However, prolonged administration of Bendamin in a tenfold therapeutic dose resulted in slight suppression of the animals’ physiological condition. This was evidenced by a 10.1 % decrease in total erythrocyte count and hemoglobin concentration, accompanied by a significant 59.8 % increase in leukocyte count (P < 0.001). Additionally, a reduction in liver function was observed, indicated by a statistically significant decrease in total protein (by 8.0 %) and urea (by 13.5 %), as well as an increase in the activity of AlAT, AsAT, and alkaline phosphatase by 31.6%, 7.4%, and 53.9 %, respectively. Significant changes in liver and spleen mass indices were also identified. Administration of a tenfold therapeutic dose of Bendamin in rats caused disturbances in the hemodynamics of various organs, accompanied by protein-related dystrophic changes with focal localization in the parenchyma of the liver, kidneys, and myocardium. These changes are interpreted as compensatory reactions of the organism to the administration of an elevated dose of the drug and are mostly reversible in nature.