Effects of sucralfate on the oral bioavailability of moxifloxacin, a novel 8-methoxyfluoroquinolone, in healthy volunteers.
OBJECTIVE
To investigate the effect of concomitant Al3+ (sucralfate) administration on the pharmacokinetics and tolerability of moxifloxacin.


METHODS
This was a single-centre, randomised, nonblinded, 2-way crossover study in healthy volunteers.


METHODS
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.
Stass
H
H
Pharma Research Centre, Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany. Heino.Stass.hs@bayer-ag.de
Schühly
U
U
Möller
J G
JG
Delesen
H
H
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001372:Aza Compounds; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D000077266:Moxifloxacin; D011804:Quinolines; D013392:Sucralfate / Q000494:pharmacology*
D000890:Anti-Infective Agents; D000897:Anti-Ulcer Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D013392:Sucralfate; D000077266:Moxifloxacin