Objective: To investigate the effect of concomitant Al3+ (sucralfate) administration on the pharmacokinetics and tolerability of moxifloxacin.
Design: This was a single-centre, randomised, nonblinded, 2-way crossover study in healthy volunteers.
Participants: 12 healthy men (age 21 to 41 years) were enrolled in the study.
Methods: The plasma and urinary pharmacokinetics of moxifloxacin were characterised up to 72 hours after single doses of moxifloxacin 400mg administered orally either alone or together with 190mg of Al3+ (Sucralfat-Ratiopharm 1000) given immediately before and at 5, 10, 15 and 24 hours after the dose of moxifloxacin. There was a 2-week washout phase between the treatments.
Results: The treatments were well tolerated. The concomitant administration of Al3+ reduced the bioavailability of moxifloxacin [geometric mean area under the concentration-time curve from zero to infinity (AUCinfinity) 12.9 versus 32.2 mg/L x h; relative bioavailability 40%, 90% confidence interval (CI) 33 to 49%] and slowed down the absorption rate [median time to maximum concentration (tmax) 3.5 versus 1.0 hours], with a reduction of the maximum plasma concentration (Cmax) fgeometric mean Cmax0.82 versus 2.83 mg/L; estimated true ratio of Cmax 29%, 90% CI 20 to 42%].
Conclusions: Concomitant ingestion with sucralfate and/or oral Al3+-containing antacids significantly reduces the bioavailability of moxifloxacin. This is compatible with reduced solubilisation as a consequence of a chelation reaction with polyvalent cations, a common finding for quinolones. Therefore, staggered administration of moxifloxacin and Al3+-containing or related cationic interactants should be considered to avoid a loss of therapeutic efficacy due to subtherapeutic plasma concentrations of the quinolone.