Safety assessment of a new anti-tuberculosis drug in silico and with the participation of healthy volunteers

• Published in: Farmakogenetika i farmakogenomika no. 1; pp. 42 - 47
• Main Authors: Savchenko, A. Yu, Ramenskaya, G. V., Kukes, V. G., Burenkov, M. S., Shilov, B. V.
• Format: Journal Article
• Language: English
• Published: 07.01.2022
• ISSN: 2686-8849; 2588-0527
• DOI: 10.37489/2588-0527-2021-1-42-47

Relevance. In connection with the increase in the number of cases of multidrug-resistant tuberculosis (MDR-TB), the search for new anti-tuberculosis drugs (ATD) is necessary. The assessment of its effect on the human body outside the aspect of the therapeutic effect is one of the main directions in the development of anti-TB drugs. Aim. Evaluation of the possible toxicity of thiosonide, a new domestic anti-TB drug, combining a consistent study of this side of the drug using a bioinformatics approach and an analysis of the results of a clinical safety study. Methods. The bioinformatic assessment was carried out using web services and models to predict the toxicity of thiosonide. The safety assessment in relation to healthy volunteers was carried out as part of a clinical study according to the protocol: «An open-label study of the pharmacokinetics, safety and tolerability of the drug thiozonide, capsule 100 mg with a single dose of increasing doses by various groups of healthy volunteers.» (2013, Permit No. 187 to conduct a clinical trial dated March 22, 2013, issued by the Ministry of Health of the Russian Federation). Results. Potential unwanted targets were identified, the predicted activity value for which was greater than 7. The results obtained indicate the likelihood of the effect of thiosonide on these protein targets and, possibly, the ability of the latter to cause side effects associated with changes in the activity of these molecules. The cytotoxic and carcinogenic effect of thiosonide is not predicted. During a clinical study, the drug thiosonide showed good tolerance and safety, since the identified adverse events did not show a definite or reliable relationship with the study drug. The resolution of all adverse events was complete, and dose escalation did not affect the number, severity of AEs and association with the study drug. Conclusion. The safety analysis of thiosonide demonstrated its good tolerability both during in silico assessment and in a study with the participation of healthy volunteers.