Studies of Acute and Chronic Toxicity of an Injectable Drug based on 3N-6-Methyl-1H Pyrimidine-2,4-Dione

Introduction. According to statistics, in 2022, 3,324.4 thousand newly diagnosed diseases with certain infectious and parasitic diseases were registered in the Russian Federation. Of these, 22.7 cases were detected for the first time per 1000 people of the population. The situation is further complicated by the emergence of new multidrug-resistant and broadly resistant strains, as well as fatal synergism with HIV./AIDS infection. 

Purpose. The development of new compounds with an adequate safety profile and with fungicidal and antiparasitic effects is necessary for effective treatment and complete cure of the disease. Assessment of the acute and chronic toxicity of a new drug is a necessary step in preclinical safety research. In this regard, the purpose of this work was to determine the acute and chronic toxicity of the developed chemical compound. 

Materials and Methods. The chemical substance pyrimidine 2,4 dione (1 amino, 6-methyl pyrimidine 2,4 dione) (PD-2,4) was synthesized on the basis of the Ural State University and was a white crystalline powder. During the study, the test sample was stored in the dark at a temperature of 5-6 ° C and dissolved in 0.7% sodium bicarbonate solution. The assessment of acute and chronic toxicity was carried out according to the guidelines for conducting preclinical studies of medicines. The experiments were reviewed in advance and approved by the UGMU Animal Ethics Committee. 

Results. When studying the acute toxicity of the drug (PD-2,4) in outbred white mice and rats of both sexes with oral or intraperitoneal administration, it was not possible to determine the average lethal dose due to the lack of death of animals in conditions of achieving the maximum possible concentrations and the maximum allowable volumes of administration. 

Conclusions. As a result of the study, it was found that PD-2,4 is low-toxic with oral and intraperitoneal administration and, according to the classification of K.K. Sidorov (1973), can be classified as a 4th class of toxicity.

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