Complexes of Ciprofloxacin with Metal Ions Contained in Antacid Drugs

Abstract

Simultaneous administration of antacids containing magnesium or aluminium and ciprofloxacin or other quinolones decreases the gastrointestinal absorption of those antibacterial agents. Current speculation about the mechanism of this interaction has focused on drug-cation chelation. The present study was designed to detect the protonation in solutions and the formation of the complex species at the pH levels typical of the gastrointestinal tract. It involves the study of ciprofloxacin in aqueous solutions containing Al3+ and (or) Mg2+ by combining the results of potentiometric and spectroscopic (1H nuclear magnetic resonance) techniques. Calculations were only performed for data in the range 4.5 < pH < 5.5 (pH levels typical of gastrointestinal tract) and the results of both methods are made self-consistent, assuming an equilibrium model including complex species MHL, MLOH (where H2L denotes ciprofloxacin and M is Al3+ or Mg2+); their formation constants are given.

Elimination of Fecal Enterobacteriaceae by Intravenous Ciprofloxacin Is not Inhibited by Concomitant Sucralfate - a Microbiological and Pharmacokinetic Study in Patients

“…Furthermore, aluminum ions contained in sucralfate as well as other cations substantially inhibit the antimicrobial activity of fluoroquinolones [15,[39][40][41]. Despite this drug interaction, the results of this study and a trial in volunteers [7] indicate that concomitant administration of sucralfate neither protects the endogenous intestinal flora, nor does it compromise the elimination of intestinal pathogens by i.v.…”

“…As the complexes probably form at a molar ratio of 1 : 1 to 3 : 1 (quinolones : cations) [50] and ciprofloxacin is only partially secreted into the intestinal lumen, a considerable excess of aluminum ions for binding of ciprofloxacin may therefore be expected. However, the aluminum ions dissociate from sucralfate mainly at low pH in the stomach [51], and ciprofloxacin is predominantly protonated at pH 1.5-3.5, which favors the formation of complexes [15]. Following intravenous administration, ciprofloxacin is mainly secreted in the jejunum and ileum [22,23].…”

“…Following oral administration of both drugs, bioavailability and antimicrobial activity of ciprofloxacin are dramatically reduced as a result of complex formation between ciprofloxacin and aluminum ions [12][13][14][15][16][17].…”

Lack of Interaction of Fluoroquinolones with Lipopolysaccharides

“…Therefore, we investigated the interaction of ciprofloxacin and moxifloxacin in the absence and presence of Mg 2؉ with whole bacteria and isolated lipopolysaccharide (LPS) from various rough mutant strains of Salmonella enterica chemotypes by applying different biophysical techniques. We found that the fluoroquinolones did not disturb the integrity of the OM and neither were incorporated into LPS monolayers nor displaced Ca 2؉ from LPS monolayers, suggesting that chelation of fluoroquinolones with divalent cations does not contribute to the antibacterial effect of fluoroquinolones.Fluoroquinolones have a tendency to chelate di-and trivalent cations (12,13,16,18,19,26,30,31,36). Therefore, it is tempting to speculate that fluoroquinolones chelate the magnesium that is associated with lipopolysaccharide (LPS) and maintains the integrity of the outer membrane (OM) (16).…”

“…Fluoroquinolones have a tendency to chelate di-and trivalent cations (12,13,16,18,19,26,30,31,36). Therefore, it is tempting to speculate that fluoroquinolones chelate the magnesium that is associated with lipopolysaccharide (LPS) and maintains the integrity of the outer membrane (OM) (16).…”