Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects

Abstract

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 (Cmax), the time to Cmax (Tmax), the area under the concentration-time curve (AUC), half-life (t1/2), clearance (CL/F), renal clearance (CLR), and cumulative amount of levofloxacin in urine (Ae) 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 Cmax was slightly reduced (Tmax, 1.0 and 2.0 h for fasting and fed conditions, respectively [P = 0.002]; Cmax, 5.9 +/- 1.3 and 5.1 +/- 0.9 microg/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 Cmax and AUC from time zero to infinity were 6.7 +/- 3.2 microg/ml and 47.9 +/- 8.4 microg x h/ml, respectively, following the administration of sucralfate compared to values of 5.9 +/- 1.3 microg/ml and 50.5 +/- 8.1 microg x h/ml, respectively, under fasting conditions. The mean t1/2, CL/F, CLR, and Ae 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.

Criteria for assessing high-priority drug-drug interactions for clinical decision support in electronic health records

“…By adjusting the administration times in the medication administration record to account for the half lives of the drugs, a time-dependent drug-drug interaction can be prevented. For example, the interaction between quinolones and multivalent cations, resulting in the decreased absorption of the former, can be avoided by a rule requiring separation in administering the drugs [30,31]. The formulation of the drug should be considered as another sub-criterion to rule out those which occur due to specific inactive ingredients present in certain formulations, e.g.…”

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

“…A high-fat breakfast combined with LVX in 24 healthy volunteers reduced the LVX C max by 14% and the AUC by 10% [246]. However, in a randomized open-label 3-way cross-over study where LVX was co-administered with juice and cereal with and without milk, the AUC was reduced by approximately 15% [247].…”

“…Four grams of sucralfate [268,269] reduced the AUC of CIP by 88–96% and 1 gram [270] by 30% when administered simultaneously. Sucralfate (1 g) also reduced the C max and AUC of OFX [238,271] by respectively 70% and 61%, and of MXF [253] by respectively 71% and 60%, but did not affect LVX [246] PK parameters in a clinical relevant matter. Pepto Bismol ® , containing Bi 3+ and Al 3+ , did not reduce the drug exposure of CIP significantly, resulting in a decrease of C max by 14% and AUC by 12% [272].…”

Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

“…The overall bioavailability of LVX following a high-fat meal was not altered despite the fact that absorption of LVX was slightly delayed by food 40. However, a study by Amsden et al concluded a lack of bioequivalence of LVX when administered in a fasting state as compared with administration with a typical breakfast of calcium-fortified orange juice and ready-to-eat cereal 41.…”