Effect of a fat- and calcium-rich breakfast on pharmacokinetics of fleroxacin administered in single and multiple doses

Abstract

The effect of a fat-and liquid-calcium-rich meal on the pharmacokinetics of single and multiple doses of fleroxacin in 20 healthy men and women was investigated in a randomized crossover fashion. Fleroxacin was administered as 400 mg daily for 3 days and as a single 400 mg dose. Concurrent administration of fleroxacin with food resulted in a statistically significant (P c 0.05) decrease in the area under the curve (13.9%Yo for multiple-dose administration, 10% for single-dose administration) and in the peak concentration (25.9% for multiple-dose administration, 27% for single-dose administration) and a lengthening of the time to peak (more than doubled for single-and multiple-dose phases). In addition, by using an equivalence criteria of 80 to 125%, the two one-sided tests procedure indicated that the mean areas under the curves for fleroxacin administered in a fed and a fasted state were statistically bioequivalent (P ' 0.05) for both the single-and multiple-dose regimens. Although a meal high in fat and containing liquid calcium reduces the peak concentration by approximately 25%, a minimal eflect on bioavailability is seen with concomitant food administration. In addition, multiple-dose bioavailability studies appear to give similar information to single-dose studies while representing the clinical setting more closely.Fleroxacin is a new fluoroquinolone anti-infective agent which is structurally related to nalidixic acid but has a broader spectrum of activity and favorable pharmacokinetic properties. This agent is a bactericidal drug whose mechanism of action is through the inhibition of an essential bacterial enzyme, DNA gyrase, which is needed for DNA replication.Fleroxacin has extensive activity against gram-negative bacteria. This high level of antimicrobial activity is combined with excellent penetration in the body fluids and tissues (2, 6). After oral administration of 400 mg, peak concentrations (Cm.) of 3 to 7 ,ug/ml have been reported (6,14). The elimination half-life (t1/2) for fleroxacin ranges from 7.9 to 13 h, the volume of distribution (Vss) ranges from 1.2 to 1.7 liters/kg, and total body clearance (CL) ranges from 5.9 to 10.6 liters/h (6, 14). The drug is approximately 23% protein bound. The oral absorption of fleroxacin is characterized by nearly complete bioavailability. From 45 to 70% of the drug is renally excreted as unchanged fleroxacin.The interaction of fluoroquinolones with food has been studied extensively. Results of pharmacokinetic studies of orally administered ciprofloxacin, lomefloxacin, enoxacin, pefloxacin, and ofloxacin have indicated variation in the pharmacokinetics of some of these agents when administered with food (4,7,9,10,18,20 547-6914. fashion (6,11,17,21). However, no studies have been conducted after administration of multiple-dose regimens. Multiple-dose regimens mimic the manner in which antibiotics are used in the clinical setting more closely than single doses do. In addition, shorter sampling periods are needed, thus decreasing costs associated with spec...

Effects of milk and food on the absorption of enoxacin.

“…Frost et al [14] studied the effect of a high fat/high calcium breakfast, containing 729 mg of calcium, on the absorption of ciprofloxacin and found no significant differences in any of the pharmacokinetic parameters. In contrast, Bertino et al [10] found that the absorption of fleroxacin was decreased 10% (P < 0.05) by concomitant ingestion of a breakfast containing 393 mg of calcium [10].…”

“…The inter-day coefficients of variation for the control samples were 3.6% (mean, 0.29 jg ml-; n = 9) and 2.9% (mean, 1.7 jig ml-; n = 9). [10] found that the absorption of fleroxacin was decreased 10% (P < 0.05) by concomitant ingestion of a breakfast containing 393 mg of calcium [10].…”

“…The effect of yoghurt on the absorption of these fluoroquinolones was slightly greater. Furthermore, Bertino et al [10] have recently reported an interaction between fleroxacin and a calcium-rich breakfast; the bioavailability and peak plasma concentration of fleroxacin were decreased by 10% and 27%, respectively [10]. Enoxacin is a broad-spectrum, synthetic fluoroquinolone antibacterial agent.…”

Effects of Sucralfate, Magnesium Oxide and Sodium Ferrous Citrate on Sparfloxacin Pharmacokinetics.

“…Previously, the interaction between the fluoroquinolones such as norfloxacin [7,17], ofloxacin [15,17], ciprofloxacin [3-6, 9, 10], lomefloxacin [11,16], DR-3355 (levofloxacin) [12] and fleroxacin [14,18] and cations has been reported. Shimada et al [19] studied the effect of antacid (dried aluminum hydroxide gel) on sparfloxacin gastrointestinal absorption, and found that it was the least inhibited by interaction with an antacid, compared with other new quinolones.…”

“…[7,17], ofloxacin [15,17], ciprofloxacin [3-6, 9, 10], lomefloxacin [11,16], DR-3355 (levofloxacin) [12], fleroxacin [14,18], and sparfloxacin [19][20][21][22][23] is decreased by concomitant administration of metal cation containing drugs. Therefore, the interaction between sparfloxacin and sucralfate can be explained primarily by the inhibition of absorption of sparfloxacin.…”