Pre-clinical toxicological study of analogue of hypothalamic hormone tsifetrilin

Abstract

Introduction. The work is devoted to preclinical toxicological research on laboratory animals tsifetrilin – a drug, an analogue of the hypothalamic hormone somatostatin, selected according to the results of studying hormonal, cytotoxic and antitumor activity. The purpose was preclinical toxicological studies of the drug’s tsifetrilin – an analogue of the hypothalamic hormone for the treatment of malignant hormone – dependent diseases. Materials and methods. Studies were carried out on 80 healthy mice hybrids (CBA × C57Bl/6J) F1 males and females, 100 non-inbred healthy mongrel male and female rats and 5 breed dogs English Beagle males and females. Preclinical toxicological studies were carried out using tsifetrilin granulate, which contained 57.3 mg of Citrate in 1 g of granulate. As a solvent, 1 % starch paste was used. In the experiments to study acute toxicity were administered orally once tsifetrilin: mice at doses of 100, 200, 300 and 600 mg/kg, to rats in doses of 100, 200, 400 and 500 mg/kg. The period of observation of the animals was 30 days. In experiments on chronic toxicity, the drug was administered orally 15 times a day: rats – total doses of 30 and 300 mg/kg; dogs – total doses of 124.5 and 622.5 mg/kg. The observation period in studies in rats was 45 days, in studies on dogs – 60 days. Results. As a result of the study of acute toxicity in mice and rats in females and males when tsifetrilin was administered at the maximum possible concentration and the maximum possible volumes, the drug did not cause death of animals, did not affect the general condition of the animals, caused no external toxicity, animals. In the study of chronic toxicity of tsifetrilin in rats and dogs with daily oral administration for 15 days, no death was observed in all the doses studied, and the drug did not cause any external toxicity. The limiting type of toxicity is not established, since the drug causes minor morphofunctional changes of varying degrees of reversibility in virtually all organs and systems of the body of rats and dogs. Based on the experimental data on functional and morphological changes in organs and tissues, it was shown that females are more sensitive to the preparation than males. Conclusion. Taking into account the functional and morphological changes in the internal organs of both rats and dogs, the studied doses of tsifetrilin are characterized as doses that cause slight minor changes-low toxic doses. Based on the analysis of the data, the initial (starting) safe dose for a person in phase I of clinical trials, which is currently being conducted, is determined.