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.


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


METHODS
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 100 equivalent to 100mg of Fe2+) administered concomitantly and again after 24 hours. There was a 1-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 reduced the bioavailability of moxifloxacin [geometric mean area under the plasma concentration-time curve 20.7 versus 34.0 mg/L x 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 (Cmax) [geometric mean Cmax 1.17 and 2.86 mg/L; estimated true ratio of Cmax 41%, 90% CI 34 to 49%].


CONCLUSIONS
Concomitant ingestion of iron supplements 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.
Stass
H
H
Pharma Research Centre, Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany. Heino.Stass.hs@bayer-ag.de
Kubitza
D
D
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001372:Aza Compounds; D001682:Biological Availability; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004347:Drug Interactions; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D000077266:Moxifloxacin; D011804:Quinolines
D000890:Anti-Infective Agents; D001372:Aza Compounds; D005296:Ferrous Compounds; D024841:Fluoroquinolones; D011804:Quinolines; C020748:ferrous sulfate; D000077266:Moxifloxacin