Complexation of fluoroquinolones with magnesium ions

Aim. To evaluate strength of magnesium ion complexes with levofloxacin and moxifloxacin.

Materials and methods. Complexation of levofloxacin, moxifloxacin, and reference ligands (ethylenediaminetetraacetate (EDTA), sodium citrate, and glycine) with magnesium ions in the range from 0.0 to 1.0 mmol / l was studied. The technique developed by the authors (patent RU 2680519 C1) was used to measure the rate of a model formation reaction of a magnesium phosphate coarse dispersion. Complexing activity of ligands was expressed in relation to EDTA activity and compared with the theoretical ion exchange equilibrium constants. The half maximal effective concentration (C50) calculated by the Michaelis − Menten equation was used to evaluate the dependence of the complexing activity on the dose.

Results. A correlation between the activity of EDTA, citrate ions, and glycine and the theoretical equilibrium constants (R = −0.87, p < 0.001) was found. In the range from 0.0 to 0.4 mmol / l, both levofloxacin and moxifloxacin showed a lesser complexing effect than EDTA (p < 0.001), and in the range from 0.6 to 1.0 mmol / l, their complexing effect was comparable (p > 0.050). The activity of fluoroquinolones did not differ at any concentration (p > 0.050), but moxifloxacin C50 (0.13 mmol / l; 95% confidence interval (CI) 0.11–0.15) was significantly lower than that of levofloxacin (0.22 mmol / l; 95% CI 0.19–0.26), (p < 0.001). Within the 0.4–1.0 mmol / l concentration range, the activity of levofloxacin was higher than that of citrate ions and glycine (p < 0.001). Complexing activity of moxifloxacin was higher than that of citrate ions within the range of 0.2–1.0 mmol / l, and in the range of 0.4–1.0 mmol / l, it was higher than that of glycine (p < 0.001).

Conclusion. The proposed method showed that the complexing activity of fluoroquinolones was close to that of EDTA and exceeded the activity of citrate ions and glycine. The complexation of fluoroquinolones may be associated with their ability to induce side effects associated with magnesium deficiency.

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