Effects of iron supplements on the oral bioavailability of moxifloxacin, a novel 8-methoxyfluoroquinolone, in humans

Objective: To investigate the effect of concomitant iron administration on the pharmacokinetics and tolerability of moxifloxacin. Design: This was a single-centre, nonblinded, randomised, 2-way crossover study in healthy male volunteers. Participants: 12 healthy males (age 19 to 41 years) were enrolled in the study. Methods: The plasma and urinary pharmacokinetics of moxifloxacin were investigated after single oral doses of moxifloxacin 400mg given either alone or together with Ferrous sulfate (Eryfer(R) 100 equivalent to 100mg of Fe2+) administered concomitantly and again after 24 hours. There was a I-week washout phase between the treatments. The plasma and urinary pharmacokinetics of moxifloxacin were characterised over the 72 hours after drug administration. Results: The treatments were well tolerated. The concomitant administration of Eryfer(R) reduced the bioavailability of moxifloxacin [geometric mean area under the plasma concentration-time curve 20.7 versus 34.0 mg/L . h; relative bioavailability 61%, 90% confidence interval (CI) 54 to 69%] and slowed down the absorption rate (median time to maximum concentration 2.79 versus 1.0 hours), with a reduction in the mean maximum concentration (C-max) [geometric mean C-max 1.17 and 2.86 mg/L; estimated true ratio of Cmax 41%, 90% CI 34 to 49%]. Conclusions: Concomitant ingestion of iron supplement significantly reduces the bioavailability of moxifloxacin. This is compatible with a reduction in solubilisation due to chelation with polyvalent cations, a common finding for quinolones. Because of the long half-life of moxifloxacin, staggered administration of moxifloxacin and potential cationic interactants should be considered to avoid a loss of therapeutic efficacy caused by subtherapeutic plasma concentrations of the quinolone.