Evaluation of the Influence of Antacids and H2 Antagonists on the Absorption of Moxifloxacin after Oral Administration of a 400mg Dose to Healthy Volunteers
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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 (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®, AUC∞ (14.7 mg/L · 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, 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 Cmax values were almost unchanged (2.55 and 2.38 versus 2.57 mg/L). The mean bioavailabilities corrected for the elimination rate constants (λz) 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.
KeywordsRanitidine Fluoroquinolones Moxifloxacin Enoxacin Relative Bioavailability
The authors are grateful to Professor A. Dalhoff for contributing the in vitro data used in the modelling studies and for his scientific support during the review of this manuscript. We also express our thanks to Dr S. Wegener for the excellent realisation of the editorial issues as well as to G. Schwarz, P. Hopfe and the medical and laboratory teams for the experimental work in this study. Parts of this paper were presented at the 20th International Congress of Chemotherapy in Sydney in 1997.[38,39]
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