Lee L J, Hafkin B, Lee I D, Hoh J, Dix R
Hoechst Marion Roussel, Inc., Bridgewater, New Jersey 08807-0800, USA.
Antimicrob Agents Chemother. 1997 Oct;41(10):2196-200. doi: 10.1128/AAC.41.10.2196.
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.
在一项针对年轻健康受试者（12名男性和12名女性）的随机、三交叉研究中，考察了食物和硫糖铝对单次口服500mg左氧氟沙星后药代动力学的影响。左氧氟沙星在三种情况下给药：空腹、进食（标准化高脂早餐后立即服用）、以及在服用左氧氟沙星2小时后空腹服用硫糖铝。通过高压液相色谱法测定血浆和尿液中左氧氟沙星的浓度。采用非房室方法估算血清中药物的最大浓度（Cmax）、达峰时间（Tmax）、浓度-时间曲线下面积（AUC）、半衰期（t1/2）、清除率（CL/F）、肾清除率（CLR）以及尿液中左氧氟沙星的累积量（Ae）。血浆中药物浓度的个体曲线在三种治疗之间差异不大。对于大多数受试者，左氧氟沙星与高脂餐同时服用的唯一一致影响是左氧氟沙星吸收延迟且Cmax略有降低（空腹和进食条件下的Tmax分别为1.0和2.0小时[P = 0.002]；空腹和进食条件下的Cmax分别为5.9±1.3和5.1±0.9μg/ml[90%置信区间 = 0.79至0.94]）。在服用左氧氟沙星2小时后给予硫糖铝，与空腹条件相比，硫糖铝似乎对左氧氟沙星的处置没有影响。与空腹条件下分别为5.9±1.3μg/ml和50.5±8.1μg·h/ml的值相比，服用硫糖铝后从零到无穷大的Cmax和AUC平均值分别为6.7±3.2μg/ml和47.9±8.4μg·h/ml。三个治疗组的平均t1/2、CL/F、CLR和Ae值相似。总之，食物使左氧氟沙星的吸收略有延迟，尽管高脂餐后左氧氟沙星的总体生物利用度未改变。最后，在抗菌药物给药2小时后给予硫糖铝时，硫糖铝不会改变左氧氟沙星的处置，从而避免了潜在的药物相互作用。
