EFFECTS OF FOOD AND SUCRALFATE ON A SINGLE ORAL DOSE OF 500 MILLIGRAMS OF LEVOFLOXACIN IN HEALTHY-SUBJECTS

The effects of food and sucralfate on the pharmacokinetics of levoflox acin following the administration of a single 500-mg oral dose were in vestigated in a randomized, three-way crossover study with young healt hy subjects (12 males and 12 females). Levofloxacin was administered u nder three conditions: fasting, fed (immediately after a standardized high-fat breakfast), and fasting with sucralfate given 2 h following t he administration of levofloxacin. The concentrations of levofloxacin in plasma and urine were determined by high-pressure liquid chromatogr aphy. By noncompartmental methods, the maximum concentration of drug i n serum (C-max), the time to C-max (T-max), the area under the concent ration-time curve (AUG), half-life (t(1/2)), clearance (CL/F), renal c learance (CLR), and cumulative amount of levofloxacin in urine (A(e)) were estimated. The individual profiles of the drug concentration in p lasma showed little difference among the three treatments, The only co nsistent effect of the coadministration of levofloxacin with a high-fa t meal for most subjects was that levofloxacin absorption was delayed and C-max was slightly reduced (T-max, 1.0 and 2.0 h for fasting and f ed conditions, respectively [P = 0.002]; C-max, 5.9 +/- 1.3 and 5.1 +/ - 0.9 mu g/ml [90% confidence interval = 0.79 to 0.94] for fasting and fed conditions, respectively). Sucralfate, which was administered 2 h after the administration of levofloxacin, appeared to have no effect on levofloxacin's disposition compared with that under the fasting con dition. Mean values of C-max and AUC from time zero to infinity were 6 .7 +/- 3.2 mu g/ml and 47.9 +/- 8.4 mu g.h/ml, respectively, following the administration of sucralfate compared to values of 5.9 +/- 1.3 mu g/ml and 50.5 +/- 8.1 mu g.h/ml, respectively, under fasting conditio ns. The mean t(1/2), CL/F, CLR, and A(e) values were similar among all three treatment groups. In conclusion, the absorption of levofloxacin was slightly delayed by food, although the overall bioavailability of levofloxacin following a high-fat meal was not altered. Finally, sucr alfate did not alter the disposition of levofloxacin when sucralfate w as given 2 h after the administration of the antibacterial agent, thus preventing a potential drug-drug interaction.