Ten normal volunteers participated in a randomized, five-way crossover study to determine the effect of concurrent enoxacin and antacid or ranitidine administration on enoxacin absorption. The bioavailability of a single oral 400-mg enoxacin dose was significantly decreased, by 73 and 49%, when Maalox TC was administered 0.5 and 2 h before enoxacin, respectively. Enoxacin bioavailability was not significantly altered when the antacid was given 8 h before or 2 h after enoxacin administration. Ranitidine, administered intravenously 2 h before enoxacin, also significantly decreased enoxacin bioavailability, by 40%. The correlation between the proximity of antacid administration and the magnitude of the decrease in enoxacin bioavailability supports complexation as the mechanism of the antacid-enoxacin interaction. However, reduction of enoxacin bioavailability by ranitidine suggests that elevated gastric pH may also play a role in the antacid-enoxacin drug-drug interaction. Preheim et al., letter), and in normal volunteers, the bioavailability of ciprofloxacin was reduced by 90% when Maalox was coadministered (Hoffken et al., Int. Symp. New Quinolones).The present study was designed to determine the effect of concurrent antacid administration on the pharmacokinetics of the quinolone antibiotic enoxacin. The influence of the time of antacid administration relative to enoxacin administration on enoxacin bioavailability was investigated to determine whether enoxacin could be given to patients receiving intensive antacid therapy. In addition, the effect of ranitidine-induced gastric-acid suppression on enoxacin absorption was also studied.
MATERIALS AND METHODSStudy design. Two males and eight females aged 20 to 40 years and weighing 54 to 78 kg participated in this nonblind, randomized, five-way crossover study. All subjects were in good health as determined by medical history, physical examination, electrocardiogram, and clinical laboratory tests. The protocol was approved by the Human Research Committee, and written informed consent was obtained from each subject.
* Corresponding author.To facilitate sample collection, all enoxacin doses (400 mg) were administered in the morning. The five treatments, given at 1-week intervals, were (i) enoxacin alone, 30 min before breakfast; (ii) enoxacin administered 8 h after a bedtime antacid dose, 30 min before breakfast; (iii) enoxacin 30 min after antacid administration, 2 h before dinner; (iv) enoxacin administered 2 h after antacid administration, 0.5 h before dinner; and (v) enoxacin administered 2 h after a 50-mg intravenous ranitidine dose, 30 min before breakfast.As per clinical use, antacid doses were administered 1 and 3 h after meals and at bedtime during treatments 2, 3, and 4. Enoxacin is typically given twice daily, in the morning before breakfast and in the evening around dinner time. Therefore, enoxacin was administered 30 min before breakfast (treatment 2) and 0.5 and 2 h before dinner (treatments 3 and 4, respectively). Each enoxacin dose was administered with ...