Improving approaches to hygienic rationing of antimicrobial drugs

Abstract

Introduction. Currently, the production of medicines, including those with antimicrobial properties, is expanding at chemical and pharmaceutical enterprises. However, scientific approaches to hygienic regulation of the content of specific antimicrobials in the air of the work area are not yet available. The study aims to substantiate approaches to predicting approximate safe levels of exposure (ASLE) to substances with a specific antimicrobial effect. Materials and methods. The scientists have carried out the research in two stages. The first stage is an experimental study of the single inhalation effect of an antibiotic clarithromycin at concentrations of 54.2; 25.4; 15.3; 9.1; 2.8 and 0.9 mg/m3 on mongrel female rats weighing 230–250 g. The authors have evaluated the indicators of toxic (morphological and functional parameters of the nervous, cardiovascular and respiratory systems, biochemical parameters of the liver and kidneys, as well as the composition of peripheral blood) and specific effects (qualitative and quantitative composition of the microbiota of the large intestine of rats). The second stage was the analysis of the database on hygienic rationing of chemicals, which consisted in searching for hygienic standards (ASLE, MPC), threshold concentrations for the general toxic (Limint) and specific (Limbact) effects of antimicrobials. Results. During the experiment, experts have established the threshold of acute inhalation exposure (Limac int) of clarithromycin at a concentration of 25.4 mg/m3 according to the total toxic effects (peripheral blood counts, liver and kidney function). When exposed to an antibiotic at a concentration of 2.8 mg/m3, there was an imbalance of the intestinal microflora in the absence of a general toxic effect, which indicated a specific and selective antimicrobial effect of the drug. Based on the analysis of literature data, the parameters of toxicometry of 21 substances with antimicrobial effect were determined, their representative sample was justified and its regression analysis was carried out. Conclusion. Based on experimental and literary data, the authors established a significantly strong correlation (r=0.729) between the values of MPC (ASLE) and the threshold of antimicrobial action (Limbact). They also developed a mathematical equation to predict safe levels of antimicrobials based on their specific and selective activity.