Spectroscopic studies on the drug–drug interaction: the influence of fluoroquinolones on the affinity of tigecycline to human serum albumin and identification of the binding site

Abstract

© 2020, Springer-Verlag GmbH Austria, part of Springer Nature. Abstract: Concomitant use of two or more drugs in therapy is becoming a more frequent phenomenon and clinically relevant drug–drug interactions at the level of binding to human serum albumin (HSA) are more often. The influence of fluoroquinolones–sparfloxacin, levofloxacin, and ciprofloxacin, on the interaction between tigecycline and HSA, was investigated in vitro by means of fluorescence and absorption spectroscopy. The results of UV–Vis and fluorescence spectroscopy showed that the fluorescence quenching of HSA was a result of the formation of new complexes through a static quenching process. The binding constants (Ka) and the number of binding sites (n) of all systems were calculated. The presence of sparfloxacin and ciprofloxacin increases and that of levofloxacin slightly decreases the binding constant of the HSA–tigecycline system. Competitive binding studies in the presence of site-specific markers showed that tigecycline was not significantly displaced by ibuprofen, but warfarin showed a significant displacement of tigecycline. These results suggest that the competitive binding of tigecycline and warfarin to HSA exists. The results confirm that the binding site of tigecycline is mainly located in Sudlow’s site I (subdomain IIA) of HSA. Graphic abstract: [Figure not available: see fulltext.].