Chem. Pharm. Bull. 55(12) 1689—1699 (2007)

chemically, may be regarded as weak substituted heterocyclic amino acids. These drugs primarily find use in the treatment of urinary and respiratory infections. Fluoroquinolones exhibit strong activity against Gram-negative and some Gram-positive bacteria, though many anaerobic strains are resistant. Fleroxacin and moxifloxacin are fluoroquinolone family members which belong to 2nd and 4th generation of these drugs, respectively (Chart 1). In clinical practice often, fluoroquinolones are administered concomitantly with other drugs which may contain metal ions. The presence of metal ions from e.g. metal based antacids or multivitamin formulations may significantly affect the activity of quinolones since they can readily bind several divalent or trivalent metal ions. Complexation alters solubility, lypophilicity, antimicrobial activity and protein binding of quinolones. The solubility of all ionic quinolone complexes is much greater than that of molecular complexes which are only sparingly soluble. Some metal–quinolone complexes show antimicrobial activity comparable to that or free quinolone but in some cases the activity is increased or lowered. Mg and Al were found to decrease the activity of quinolones whereas Fe and Zn complexes exhibit greater activity. Clinical investigations have shown that concomitant intake of fluoroquinolones and aluminum-containing antacids results in reduced maximal plasma concentration accompanied by the decrease in AUC. Both effects lead to the decreased bioavailability of the drug, down to 40%. To explain the observed phenomenon one may take into account that number of forms in which quinolones may exist in solution (neutral, cationic, zwitterionic and anionic) as well as vicinity of carbonyl and carboxyl groups make them the suitable ligands for hard acid metal ions, in particular for Al . On the other hand the Al ion forms the complexes of the highest stability with the ligands containing hard donor groups (i.e. basic negatively charged oxygen atoms). Thus, the reduced bio-availability of the quinolones in the presence of Al may be explained by chelation between Al ion and the 3-carboxyl and 4-oxo functional groups of the quinolones. Besides the reduction of the bioavailability and activity of quinolones the interactions between aluminum ion and quinolones have significant effect on metabolism of aluminum in human organism. Numerous investigations have shown that aluminum can be regarded as detrimental and in particular neurotoxic element. Patients with high tissue and serum level of aluminum may develop blood, bone or brain diseases which may be linked to the excess of aluminum. The presence of fluoroquinolones may influence Al absorption through the formation of Al-complexes which may be stable enough to produce a sufficient decrease in free Al concentration so that a significant amount of the poorly soluSolution Equilibria between Aluminum(III) Ion and some Fluoroquinolone Family Members. Spectroscopic and Potentiometric Study