Influence of metal cations on the solubility of fluoroquinolones.

Although a clinically relevant interaction between a fluoroquinolone and a metal cation was first described more than 20 years ago the biopharmaceutical mechanism of this interaction is still not understood. One of the obvious disagreements in the literature is about the effect of metal cations on the solubility of fluoroquinolones. Namely, metal cations are reported to increase the solubility of fluoroquinolones as well as to decrease it and thus cause the lowered bioavailability. Thus in this work the solubility of ciprofloxacin, norfloxacin and ofloxacin and the effect of metal cations on the solubility of these fluoroquinolones in aqueous media of different pH values were reevaluated. The results clearly show that the metal cations either do not affect or even increase the solubility of fluoroquinolones. Thus they surely do not influence the bioavailability of these drugs by decreasing their solubility. Additionally, possible explanations for the contradictory results reported in the literature are given.

Polarised transport of monocarboxylic acid type drugs across rat jejunum in vitro: the effect of mucolysis and ATP-depletion.

The transport characteristics of monocarboxylic acid type drugs (ketoprofen, ibuprofen and gemfibrozil) across the excised jejunal segments and artificial (octanol impregnated) membrane in side-by-side diffusion cells were studied. All three model drugs permeated faster across the intestinal tissue in the mucosal-to-serosal direction than in the opposite direction. No polarised transport of tested drugs was observed when the mucosal side of the intestine was treated with mucus disrupting agent, L-cysteine 1% (w/v), which significantly increased the microclimate pH at the mucosal surface of the intestine. Similar effects on the transport characteristics of model drugs and microclimate pH were observed when metabolic inhibitor, sodium azide (10mM), was present in the incubation medium. Furthermore, the direction of proton gradient across the artificial membrane was shown to significantly influence the transport of model drugs across this membrane. The results of this study indicate that the inwardly directed proton gradient maintained by the acidic microclimate pH at the intestinal surface could be considered as a driving force for the transport of monocarboxylic acid type drugs across the intestinal epithelia and could explain rapid absorption of these drugs after oral application.