Effect of food on the pharmacokinetics of a single oral dose of moxifloxacin 400mg in healthy male volunteers

Objective: To investigate the effects of concomitant food intake on the pha rma cokinetics of a single oral dose of moxifloxacin 400mg. Design: This was a randomised 2-way nonblinded crossover study in healthy v olunteers. Participants: 18 young, healthy, male volunteers were enrolled in the study , of whom 16 were considered evaluable for the pharmacokinetic analysis. Methods: Moxifloxacin was given under 2 conditions separated by a 1-week wa shout period: fasted and fed (immediately after a standardised high fat bre akfast). Concentrations of moxifloxacin in serum were determined by a valid ated high performance liquid chromatography procedure with fluorescence det ection. Outcome measures: Pharmacokinetic parameters such as maximum concentration (C-max), time to reach C-max (t(max)), area under the concentration-time cu rve from zero to 48 hours (AUC(48h)), AUC from zero extrapolated to infinit y (AUC,) and elimination half-life (t(1/2z)) were estimated using noncompar tmental methods. The natural logarithms of AUC and C-max were analysed usin g analysis of variance. Bioequivalence of the 2 treatments was determined a t the 5% significance level with the two 1-sided tests procedure and limits of 80% and 125% for AUC and 70 to 143% for C-max. Results: The mean serum concentration versus time profiles were similar bet ween the 2 treatments. The geometric mean AUC(infinity) values under fed an d fasted conditions were almost identical, 37.7 versus 38.5 mg/L . h, respe ctively [90% confidence interval (CI) of the ratio of fed versus fasted bas ed on geometric least-square means was 0.95, 1.00]. Geometric mean C-max va lues were slightly reduced by food, 2.5 versus 2.8 mg/L, respectively (90% CI of fed versus fasted based on geometric least-square means was 0.78, 0.9 8). The absorption of moxifloxacin seems to be mildly delayed because of th e effect of food; the median t(max) values were 1.0 and 2.5 hours for faste d and fed conditions, respectively. The single oral dose of moxifloxacin 40 0mg was well tolerated when taken with and without food. Conclusions: The criteria for bioequivalence with respect to C-max and AUC( infinity) were met when moxifloxacin 400mg was given on an empty stomach or immediately after a high fat meal. Moxifloxacin may be given to patients w ith or without food.