Evaluation of the influence of antacids and H2 antagonists on the absorption of moxifloxacin after oral administration of a 400mg dose to healthy volunteers.
OBJECTIVE
To determine the effect of concomitant administration of the antacid Maalox 70 or the histamine H2 receptor antagonist ranitidine on the bioavailability of moxifloxacin.


METHODS
These were nonblinded, randomised, crossover studies performed in healthy volunteers.


METHODS
24 healthy males aged 22 to 39 years (study 1; n = 12) and 24 to 43 years (study 2; n = 12) were included in these studies.


METHODS
In study 1, 12 participants received ranitidine 150mg twice daily during a 3-day pretreatment phase and 1 tablet of ranitidine together with a single 400mg dose of moxifloxacin on the profile day. In study 2, 12 participants received a single 400mg dose of moxifloxacin alone (treatment A), simultaneously with Maalox 70 10ml (treatment B), or with Maalox 70 10ml given 4 hours before (treatment C) or 2 hours after (treatment D) the fluoroquinolone. In treatments B, C and D, administration of the antacid (10ml, 1 hour after each meal) was continued for 2 days. Plasma and urine samples were obtained for determination of the pharmacokinetic parameters of moxifloxacin.


RESULTS
Coadministration of moxifloxacin with ranitidine showed lack of interaction for area under the plasma concentration-time curve extrapolated to infinity (AUCinfinity) [35.5 versus 34.3 mg/L x h with versus without ranitidine; relative bioavailability 103%, 90% confidence interval (CI) 97.7 to 109.3%] and maximum plasma concentration (Cmax) [2.98 versus 2.76 mg/L with versus without ranitidine; ratio 107.9%, 90% CI 90.5 to 128.6%]. When moxifloxacin was given simultaneously with Maalox 70, AUCinfinity ( 14.7 mg/L x h) and Cmax (1.00 mg/L) were reduced by approximately 60%. When the antacid was given 4 hours before or 2 hours after the fluoroquinolone, AUCinfinity values (28.0 and 26.7 versus 34.3 mg/L x h) were moderately reduced (by <27%), terminal elimination half-life values declined by approximately 24% (9.4 and 9.3 versus 12.3 hours) compared with moxifloxacin alone and Cmax values were almost unchanged (2.55 and 2.38 versus 2.57 mg/L). The mean bioavailabilities corrected for the elimination rate constants (lambdaz) were 101% (antacid given 4 hours before moxifloxacin) and 98% (antacid given 2 hours after moxifloxacin), indicating that Maalox 70 may interfere with the gastrointestinal recirculation of moxifloxacin.


CONCLUSIONS
The bioavailability of moxifloxacin is not affected by concurrent administration of ranitidine. Absorption of moxifloxacin is impaired by concomitant administration of aluminium- and magnesium-containing antacids and administration of these agents should be staggered. An interval of 2 hours before or 4 hours after taking the antacid ensures that the effect of the interaction is not clinically relevant.
Stass
H
H
Pharma Research Centre, Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany. Heino.Stass.hs@bayer-ag.de
Böttcher
M F
MF
Ochmann
K
K
D000284:Administration, Oral; D000328:Adult; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000863:Antacids / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001372:Aza Compounds; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D024841:Fluoroquinolones; D006207:Half-Life; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008276:Magnesium Hydroxide / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D000077266:Moxifloxacin; D011804:Quinolines; D011899:Ranitidine / Q000494:pharmacology*
D000863:Antacids; D000890:Anti-Infective Agents; D001372:Aza Compounds; D004338:Drug Combinations; D024841:Fluoroquinolones; D006635:Histamine H2 Antagonists; D011804:Quinolines; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D000536:Aluminum Hydroxide; D011899:Ranitidine; D008276:Magnesium Hydroxide; D000077266:Moxifloxacin