[A dynamic system for the in vitro study of the kinetics of the antimicrobial effect of antibiotics in pharmacokinetic changes in their concentration].

The present approaches to in vitro investigation of the kinetics of the antibiotic antimicrobial effect are based on its recording at one or another constant concentration of the drugs. The regularities revealed under such conditions do not usually reflect the peculiar effect of the drugs in vivo, since with the use of the routine schemes of dosing the drug levels in the body fluids always vary. For investigation of the kinetics of the antimicrobial effect of antibiotics at their varying levels, a universal dynamic system providing in vitro simulation of the pharmacokinetic profiles of the drugs in blood and tissues was developed. The system is based on the controlled dilution of the medium containing an antibiotic and microbial cells. the dynamic system allows simulation of any kinetic profile of the drugs with regard to the constants of the linear pharmacokinetic N-compartmental model. The trial of the dynamic system as applied to the antimicrobial effect of sisomicin on strain A 20 363 of E. coli revealed significant differences in the effect of the drug, when its bioexponential pharmacokinetic profile was simulated in a one-compartmental model with exponential absorption and a constant concentration of the antibiotic. The check determinations of the antibiotic concentration in the main flask of the system showed that the system provided high accuracy simulation of the required antibiotic levels.