Evaluation of the Influence of Antacids and H₂ Antagonists on the Absorption of Moxifloxacin after Oral Administration of a 400mg Dose to Healthy Volunteers

To determine the effect of concomitant administration of the antacid Maalox 70® or the histamine H₂ receptor antagonist ranitidine on the bioavailability of moxifloxacin.

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

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.

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.

Coadministration of moxifloxacin with ranitidine showed lack of interaction for area under the plasma concentration-time curve extrapolated to infinity (AUC∞) [35.5 versus 34.3 mg/L · h with versus without ranitidine; relative bioavailability 103%, 90% confidence interval (CI) 97.7 to 109.3%] and maximum plasma concentration (C_max) [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®, AUC∞ (14.7 mg/L · h) and C_max(1.00 mg/L) were reduced by approximately 60%. When the antacid was given 4 hours before or 2 hours after the fluoroquinolone, AUC∞ values (28.0 and 26.7 versus 34.3 mg/L · 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 C_max values were almost unchanged (2.55 and 2.38 versus 2.57 mg/L). The mean bioavailabilities corrected for the elimination rate constants (λ_z) 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.

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.