Toxicological properties of a new anti-tuberculosis drug from the group of diarylquinolines

Background. There are known adverse effects of anti-tuberculosis drugs (ATDs) that can limit the effectiveness of treatment: nephrotoxicity of aminoglycosides, cardiotoxicity of fluoroquinolones, gastrointestinal toxicity of ethionamide or para-aminosalicylic acid, toxicity of cycloserine in relation to the central nervous system. Meanwhile, the increase in the number of cases of multidrug-resistant tuberculosis (MDR-TB) is the basis for the search for new ATDs that are safe for long-term use in the context of MDR-TB therapy. Objective. Evaluation of subchronic toxicity of thiozonide, a new domestic anti-tuberculosis drug from the group of diarylquinolines. Methods. The subchronic toxicity of two forms of the thiozonide (P1 and P2 - different pairs of stereoisomers) was studied in an experiment on dogs for 3 months. Animals received doses ranging from human therapeutic dose (HTD) equivalent up to 10-times-equivalent-HTD (10 HTD). Results. The drug in the studied doses did not cause significant changes in appearance, behavioral reactions, and food and water consumption. There were no changes in the cellular composition of peripheral blood, hemostasis indicators. There were a transient elevated liver transaminase levels in the serum of animals receiving 10 HTD, a decrease in the of serum proteins levels in the same groups. Histological changes were insignificant and reversible. Conclusion. Thus, the new anti-tuberculosis drug thiozonide does not have toxic properties limiting its long-term use, that suggests the prospect of using this drug for long-term treatment of tuberculosis.

thiozonide, subchronic toxicity, dogs