MECHANISTIC STUDY OF INHIBITION OF LEVOFLOXACIN ABSORPTION BY ALUMINUM HYDROXIDE

The mechanisms of reduction in absorption of levofloxacin (LVFX) by co administration of aluminum hydroxide were studied. The partition coeff icient of LVFX (0.1 mM) between chloroform and phosphate buffer (pH 5. 0) was reduced by 60 to 70% with the addition of metal ions such as Cu 2+, Al3+, and Fe2+ (0.8 mM), which indicated the formation of LVFX-met al ion chelates. However, there was no significant difference in absor ption from rat intestine between the synthetic LVFX-Al3+ (1:1) chelate (6.75 mM) and LVFX (6.75 mM) in an in situ recirculation experiment. On the other hand, Al(NO3)3 (1.5 mM) significantly inhibited the absor ption of LVFX (1.5 mM) by 20% of the control in the in situ ligated lo op experiment, in which partial precipitation of aluminum hydroxide wa s observed in the dosing solution. Data for adsorption of LVFX and ofl oxacin (OFLX) from aqueous solution by aluminum hydroxide were shown t o fit Langmuir plots, and the adsorptive capacities (r(max)) and the K values were 7.0 mg/g and 1.77 x 10(4) M-1 for LVFX and 7.4 mg/g and 1 .42 x 10(4) M-1 for OFLX, respectively. The rate of adsorption of seve ral quinolones (50 muM) onto aluminum hydroxide (2.5 mg/ml) followed t he order norfloxacin (NFLX) (72.0%) > enoxacin (ENX) (61.0%) > OFLX (4 7.2%) almost-equal-to LVFX (48.1%). The elution rate of adsorbed quino lones with water followed the rank order LVFX (17.9%) almost-equal-to OFLX (20.9%) almost-equal-to ENX (18.3%) > NFLX (11.9%). These results strongly suggest that adsorption of quinolones by aluminum hydroxide reprecipitated in the small intestine would play an important role in the reduced bioavailability of quinolones after coadministration with aluminum-containing antacids.