Evaluation of the influence of antacids and H-2 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 ant acid Maalox 70(R) or the histamine H-2 receptor antagonist ranitidine on th e bioavailability of moxifloxacin. Design: These were nonblinded, randomised, crossover studies performed in h ealthy volunteers. Participants: 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 part icipants received a single 400mg dose of moxifloxacin alone (treatment A), simultaneously with Maalox 70(R) 10ml (treatment B), or with Maalox 70(R) 1 0ml given 4 hours before (treatment C) or 2 hours after (treatment D) the f luoroquinolone. In treatments B, C and D, administration of the antacid (10 ml, 1 hour after each meal) was continued for 2 days. Plasma and urine samp les were obtained for determination of the pharmacokinetic parameters of mo xifloxacin. Results: Coadministration of moxifloxacin with ranitidine showed lack of in teraction for area under the plasma concentration-time curve extrapolated t o infinity (AUC(infinity)) [35.5 versus 34.3 mg/L . h with versus without r anitidine; 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(R), AUC(infinity) (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(infinity) values (28.0 and 26.7 versus 34.3 mg/L . h) were moderately r educed (by <27%), terminal elimination half-life values declined by approxi mately 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). Th e mean bioavailabilities corrected for the elimination rate constants (<lam bda>(z)) were 101% (antacid given 4 hours before moxifloxacin) and 98% (ant acid given 2 hours after moxifloxacin), indicating that Maalox 70(R) may in terfere with the gastrointestinal recirculation of moxifloxacin. Conclusions: The bioavailability of moxifloxacin is not affected by concurr ent 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 h ours before or 4 hours after taking the antacid ensures that the effect of the interaction is not clinically relevant.