EVALUATION OF CEPHALOSPORIN’S LIPOPHILIC PROPERTIES

Abstract

As a part of the study, a comparative analysis of different generations three representative’s lipophilic properties of cephalosporin antibiotics, namely cefazolin, cefotaxime and cefepime, was carried out. Lipophilicity is a very important physicochemical property of medicinal substances, since it determines their ability to pass through protective barriers, distribute, accumulate in tissues and body fluids, be broken down and excreted, which, in turn, affects the manifestation of antibacterial activity and the cytotoxic effect of antibiotics. During the experiment, a series of drugs aqueous solutions were prepared, then the antibiotics were extracted with highly purified olive oil, after which the aqueous phase was taken and the osmolality value for it was determined. Based on the calibration dependences of the osmolality value on the concentration of the antibiotic in the aqueous phase after extraction, the logarithms of the distribution coefficients in the «oil/water» system were calculated, which is a numerical indicator of the lipophilicity of substances. Using the capabilities of the online platform «Molinspiration Cheminformatics Software», the theoretical values of the studied drugs distribution coefficients logarithms were also determined, and the theoretical values correlated with the experimental ones. Based on the data obtained, it was revealed that the studied antibiotics have low lipophilicity, which decreases in the order: cefotaxime > cefazolin > cefepime. The work also assessed the relationship between solution pH and lipophilic properties. Pearson's r-coefficients between pH and antibiotic concentrations in oil after extraction of cefotaxime and cefazolin show a weak inverse relationship between the studied parameters. For cefepime solutions, a similar linear correlation coefficient demonstrates a direct high relationship between the pH of the solution and the lipophilicity of the antibiotic. The results of the study can be taken into account during antibiotic therapy with appropriate cephalosporins, as well as when creating a new generation of antibiotics. For citation: Kataeva N.N., Naronova N.A., Golitsyna K.O., Belokonova N.A., Shulepova K.E. Evaluation of cephalosporin’s lipophilic properties. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 7. P. 55-62. DOI: 10.6060/ivkkt.20246707.7018.