Effects of Food and Sucralfate on a Single Oral Dose of 500 Milligrams of Levofloxacin in Healthy Subjects (original) (raw)

The effects of food and sucralfate on the pharmacokinetics of levofloxacin following the administration of a single 500-mg oral dose were investigated in a randomized, three-way crossover study with young healthy subjects (12 males and 12 females). Levofloxacin was administered under three conditions: fasting, fed (immediately after a standardized high-fat breakfast), and fasting with sucralfate given 2 h following the administration of levofloxacin. The concentrations of levofloxacin in plasma and urine were determined by high-pressure liquid chromatography. By noncompartmental methods, the maximum concentration of drug in serum (C max ), the time to C max (T max ), the area under the concentration-time curve (AUC), half-life (t 1/2 ), clearance (CL/F), renal clearance (CL R ), and cumulative amount of levofloxacin in urine (A e ) were estimated. The individual profiles of the drug concentration in plasma showed little difference among the three treatments. The only consistent effect of the coadministration of levofloxacin with a high-fat 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 fed conditions, respectively [P ‫؍‬ 0.002]; C max , 5.9 ؎ 1.3 and 5.1 ؎ 0.9 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 condition. Mean values of C max and AUC from time zero to infinity were 6.7 ؎ 3.2 g/ml and 47.9 ؎ 8.4 g ⅐ h/ml, respectively, following the administration of sucralfate compared to values of 5.9 ؎ 1.3 g/ml and 50.5 ؎ 8.1 g ⅐ h/ml, respectively, under fasting conditions. The mean t 1/2 , CL/F, CL R , 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, sucralfate did not alter the disposition of levofloxacin when sucralfate was given 2 h after the administration of the antibacterial agent, thus preventing a potential drug-drug interaction.