Decrease in ciprofloxacin absorption by polyvalent metal cations is not fully attributable to chelation or...

Area of Science:

• Pharmacology
• Drug Interactions
• Gastrointestinal Absorption

Background:

• New quinolone antibiotics (NQs) exhibit reduced absorption when co-administered with polyvalent metal cation products.
• This interaction is hypothesized to involve chelate formation and physicochemical adsorption of NQs to metal cations.

Purpose of the Study:

• To elucidate the mechanisms behind the drug interaction between NQs and polyvalent metal cations.
• To investigate the impact of aluminum (Al3+) and magnesium (Mg2+) on ciprofloxacin (CPFX) membrane permeation.
• To characterize the adsorption of CPFX to polyvalent metal cation products under physiological conditions.

Main Methods:

• Utilized Caco-2 cell monolayers to model human intestinal absorption.
• Assessed the effect of Al3+ and Mg2+ on ciprofloxacin permeation across the Caco-2 cell barrier.
• Evaluated the adsorption of ciprofloxacin to polyvalent metal cation products at physiological pH.

Main Results:

• Al3+ and Mg2+ partially reduced ciprofloxacin permeation across Caco-2 cells by up to 30% and 60% of control, respectively.
• No significant physicochemical adsorption of ciprofloxacin to polyvalent metal cation products was detected under physiological conditions.
• Chelate formation appears to be a contributing factor, but does not fully account for the observed reduction in NQ absorption.

Conclusions:

• Chelate formation between new quinolone antibiotics and polyvalent metal cations partially explains reduced drug absorption.
• Adsorption to metal cations does not significantly contribute to this interaction under physiological conditions.
• The investigated mechanisms partially explain, but do not fully account for, the clinical drug interaction between NQs and polyvalent metal cations.