ИССЛЕДОВАНИЕ ФАРМАКОКИНЕТИКИ ТВЕРДОДИСПЕРСНОЙ И КРИСТАЛЛИЧЕСКОЙ ФОРМ АНТИВИРУЛЕНТНОГО СРЕДСТВА ФТОРТИАЗИНОН У КРЫС

Abstract

Prevalent drug resistance of pathogenic bacteria is a major concern for healthcare. Decreased bacterial susceptibility to antibiotics reduces treatment efficiency, putting lives of patients at risk. To overcome this issue, a novel anti-virulence drug Fluorothiazinon (FT) was developed. The drug inhibits type three secretion system and flagella motility of many Gram-negative bacteria. It showed therapeutic activity against a number of pathogenic microorganisms, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Chlamydia trachomatis and Salmonella enterica Typhimurium among others. To find appropriate form for subsequent drug development solid dispersion and crystalline forms of FT were manufactured. In this study we aimed to investigate pharmacokinetics of FT in two forms to find the formulation with higher bioavailability. For comparative pharmacokinetics study rats were allocated to receive a single oral dose 50 mg/kg of the drug in either solid dispersion or crystalline forms. Determination of FT and its metabolite was carried out by high-performance liquid chromatography – tandem mass-spectrometry analysis. Our results show that the solid dispersion form of Fluorothiazinon has a higher oral bioavailability of 235.4% compared to the crystalline form in rats. Therefore, solid dispersion form was demonstrated to be more suitable for dug development to have enhanced bioavailability, leading to increased absorption and possible improved therapeutic potential of the developed drug based on pharmacokinetics data.