Affiliation:
1. Research-and-manufacturing company “HOME OF PHARMACY”
2. Scientific Center of Biomedical Technology of the Federal Medical-Biological Agency of Russia
Abstract
Several treatment regimens with antituberculosis medicinal products are available for tuberculosis. Thiozonide is a newly developed original antimicrobial agent that exhibits bacteriostatic activity against Mycobacterium tuberculosis strains H37Rv, CN-37, CN-40, and MS-115.The aim of the study was to investigate the embryotoxic, foetotoxic, and teratogenic effects of thiozonide in pregnant rabbits.Materials and methods. The study involved 66 pregnant rabbits (4 groups of 16–17 animals each). The rabbits received oral thiozonide from day 6 to day 19 of gestation at doses of 20.6 mg/kg (1 TD (therapeutic dose)), 103 mg/kg (5 TDs), and 206 mg/kg (10 TDs). The control group received a 1% starch solution. The authors conducted a macroscopic examination of the reproductive organs and a histological evaluation of the placenta in eutha nised pregnant rabbits. Live foetuses underwent a check for developmental abnormalities, a skeletal development evaluation with a modified Dawson’s method, and a histologic examination of the internal organs.Results. The study showed no clinical signs of toxicity and no mortality associated with thiozonide in pregnant rabbits across all dose groups. Macroscopic and histological examinations revealed no pathological changes in the reproductive organs of pregnant rabbits. The evaluation of embryotoxic and foetotoxic effects did not identify any differences between the foetuses of the animals assigned to different doses of thiozonide and the control group. The authors found no developmental abnormalities in the foetuses. Examinations of foetal skeleton development and internal organ condition identified no differences between the groups and no abnormalities. The authors registered the death of all foetuses (late resorption) in one rabbit from the 206 mg/kg group. Therefore, the 103 mg/kg dose (5 TDs) was selected as a reasonable No Observed Adverse Effect Level (NOAEL).Conclusions. Thiozonide has no embryotoxic, foetotoxic, or teratogenic effects.
Reference14 articles.
1. Vasilyeva IА, Testov VV, Sterlikov SА. Tuberculosis situation in the years of the COVID-19 pandemic — 2020–2021. Tuberculosis and Lung Diseases. 2022;100(3):6–12 (In Russ.). https://doi.org/10.21292/2075-1230-2022-100-3-6-12
2. Sterlikov CA, Rusakova LI, Son IM. Extensively drug-resistant tuberculosis treatment outcomes: results of the three-year observation. Current Problems of Health Care and Medical Statistics. 2018;(2):14–27 (In Russ.).
3. Sаvchenko AYu, Burenkov MS, Bаydin PS, Rаmenskаya GV, Perovа NV, Kukes VG. Study of genotoxic properties of thiosonide. Tuberculosis and Lung Diseases. 2021;99(6):22–7 (In Russ.). http://doi.org/10.21292/2075-1230-2021-99-6-22-27
4. Bocharova IV, Burenkov MS, Lepekha LN, Smirnova TG, Chernousova LN, Demikhova OV. Preclinical studies of the specific activity of the new antituberculosis drug thiozonide. Tuberculosis and Lung Diseases. 2014;(6):46–50 (In Russ.). EDN: SLSSBX
5. Savchenko AU, Ramenskaya GV, Bourenkov MS. The safety and tolerability study of tiozonid in single dose with it increasing. Good Clinical Practice. 2016;(3):43–8 (In Russ.).