Deferasirox and Ciprofloxacin: Potential Ternary Complex Formation With Ferric Iron, Pharmacodynamic, and Pharmacokinetic Interactions.

Abstract

The main aim of this work was to assess the potential formation of ternary chelate complexes, involving deferasirox (DFX), ciprofloxacin (CP), and ferric iron. The coadministration of CP along with DFX might modulate its efficacy, so it is important that it be investigated. A ternary complex involving DFX, CP, and iron (DFX-CP-Fe) was prepared and characterized. Theoretical chemistry calculations were performed to measure the equilibrium constants of complexes. Two groups of rats were exposed to DFX or DFX with CP. The level of DFX in plasma was measured, and histological assessments of relevant organs were made. Levels of iron in selected tissues were measured. The formation of ternary complexes was confirmed. Two ternary complexes are thermodynamically favored. The first one of ratio (DFX:CP:Fe) was shown to be favorable with an equilibrium constant of 2 × 10⁷. The second one with ratio (DFX:CP:2Fe) is more thermodynamically favored with an equilibrium constant of 2.0 × 10⁶⁰. Rats treated with a combination of DFX and CP exhibited lower levels of iron in dried red blood cells in comparison to those treated with DFX alone (p value = 0.012). They also exhibited lower levels of DFX in plasma. Histological assessments of the relevant tissues showed a clear difference in the level of deposited iron in the spleen. In conclusion, ternary complexes are formed, and some with exceptionally high constants. The obtained data indicate a potentially favorable role of CP because while it resulted in a decrease in the level of DFX, it pharmacodynamically produced more effect.