Effect of divalent and trivalent metal ions on artificial membrane permeation of fluoroquinolones

Abstract

The purpose of the present study was to evaluate the predictability of PAMPA for the effect of metal ions on the bioavailability of fluoroquinolones (FQ). Eleven FQs and seven metal ions were employed in this study. The PAMPA membrane consisted of a 10 % soybean lecithin (SL) – decane solution. A drug solution in MES buffer with or without a metal ion (added as a chloride salt) was added to the donor compartment. In the absence of metal ions, FQ showed relatively high permeability (> 5 × 10^-6 cm/sec) in SL-PAMPA despite their hydrophilic and zwitterionic properties. As the PAMPA permeability ratio with/without metal ions became smaller, the urinary excretion and AUC ratios tended to be smaller, suggesting that SL-PAMPA is a suitable in vitro model to evaluate the potential effect of metal ions on the bioavailability of FQ. However, the reduction in AUC and urinary excretion was overestimated for low solubility metal ion formulations (dried aluminum hydroxide gel and La₂(CO₃)₃・8H₂O). In such cases, the dissolution of the metal ion formulations and the permeation of FQs should be simultaneously evaluated.