The Effect of Decreasing the Toxicity of Fluoroquinolones in Dissolution Media of Different Composition

Abstract

Abstract. The purpose of this work is to evaluate the effectiveness of reducing the toxicity of fluoroquinlone (FTQ) drugs. For this the Spirotox original method was used in combination with the model scheme of the enzymatic kinetics of Michaelis-Menten. Dissolution media of different nature and isotopic composition are considered as factors contributing to the reduction of the FTQ toxicity. The nature of a solvent with a different D/H ratio demonstrates the development of the kinetic isotope effect (KIE) during the course of biochemical processes ("light" water), as well as detoxifying properties (a complex of humic and fulvic acids, HFA). By the method of tangents to the graph of the“tL,sec – -lgC” function, an intersection with the ox axis corresponding to Ctox, mol·L-1 was found at the approximation point. It has been shown that the FTQ dilution with "light" water (with a reduced deuterium content, ≤ 1 ppm) or a complex of humic and fulvic acids contributes to an increase in the cells lifetime by 3-4 times compared with purified water. When selecting the highest value of the Pearson coefficient from the graphical dependence "tL – 1/Ln", as a result of extrapolation to x=0 and y=0, the enzymatic kinetic parameters were determined – Keq (by the negative segment on the ox axis) and fm (by the segment on the oy axis). The obtained values were for levofloxacin drug: Keq =3.99 ·10-2 mol·L-1, fm= 2.17 ·10-3 s-1 (dilution with purified water), Keq=1.12·10-1 mol·L-1, fm=4.62·10-2 s-1 (dilution with "light" water), Kp=6.37·10-1 mol·L-1, fm=1.61·10-2 s-1 (dilutions with HFA); for moxifloxacin drug: Keq=3.87·10-3 mol·L-1, fm= 7.87 ·10-2 s-1 (dilution with purified water), Keq=7.50·10-3 mol·L-1, fm=1.75·10-2 s-1 (dilution with "light" water), Keq=9.89·10-8 mol·L-1, fm=2.06·10-2 s-1 (dilution with GFC). The results obtained can be used in the pharmaceutical industry for the manufacture of medicines with an improved pharmacological profile.