Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats

Abstract

Glycopeptide antibiotics have side effects that limit their clinical use. In view of this, the development of glycopeptides with improved chemotherapeutic properties remains the main direction in the search for new antibacterial drugs. The objective of this study was to evaluate the toxicological characteristics of new semi-synthetic glycopeptide flavancin. Acute and chronic toxicity of antibiotic was evaluated in Wistar rats. The medium lethal dose (LD50) and the maximum tolerated doses (MTD) were calculated by the method of Litchfield and Wilcoxon. In the chronic toxicity study, the treatment regimen consisted of 15 daily intraperitoneal injections using two dosage levels: 6 and 10 mg/kg/day. Total doses were equivalent to MTD or LD50 of flavancin, respectively. The study included assessment of the body weight, hematological parameters, blood biochemical parameters, urinalysis, and pathomorphological evaluation of the internal organs. The results of the study demonstrated that no clinical-laboratory signs of toxicity were found after 15 daily injections of flavancin at a total dose close to the MTD or LD50. The pathomorphological study did not reveal any lesions on the organ structure of animals after low-dose administration of flavancin. Thus, flavancin favorably differs in terms of toxicological properties from the glycopeptides currently used in the clinic.

Experimental Evaluation of the Hypersensitivity Reactions of a New Glycopeptide Antibiotic Flavancin in Animal Models

“…In the course of our previous research focused on the development of new glycopeptide antibiotics with improved toxic properties and targeting antibiotic-resistant pathogens, we identified a promising candidate, eremomycin aminoalkylamide, called flavancin, for further in-depth preclinical studies. Flavacin showed advantages over the natural antibiotics vancomycin and eremomycin both in specific antibacterial activity and toxicological properties [17,18]. However, despite these positive findings, important aspects of flavancin, such as its potential to induce hypersensitivity reactions, remained unexplored.…”