Chien S C, Rogge M C, Gisclon L G, Curtin C, Wong F, Natarajan J, Williams R R, Fowler C L, Cheung W K, Chow A T
The R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869, USA.
Antimicrob Agents Chemother. 1997 Oct;41(10):2256-60. doi: 10.1128/AAC.41.10.2256.
The pharmacokinetics of once-daily oral levofloxacin (study A) or intravenous levofloxacin (study B) in 40 healthy male volunteers were investigated in two separate randomized, double-blind, parallel-design, placebo-controlled studies. Levofloxacin at 500 mg or placebo was administered orally or intravenously as a single dose on day 1; daily oral or intravenous dosing resumed on days 4 to 10. In a third study (study C), the comparability of the bioavailabilities of two oral and one intravenous levofloxacin formulations were investigated with 24 healthy male subjects in an open-label, randomized, three-way crossover study. Levofloxacin at 500 mg as a single tablet or an intravenous infusion was administered on day 1; following a 1-week washout period, subjects received the second regimen (i.e., the other oral formulation or the intravenous infusion); the third and final regimen was administered following a 1-week washout period. The concentrations of drug in plasma and urine were measured by validated high-pressure liquid chromatography methods. Pharmacokinetic parameters were estimated by noncompartmental methods. In both study A (oral levofloxacin) and study B (intravenous levofloxacin), steady state was attained within 48 h after the start of the multiple dosing on day 4. Levofloxacin pharmacokinetics were linear and predictable for the single and multiple 500-mg, once-daily oral and intravenous dosing regimens, and the values of the pharmacokinetic parameters for the oral and intravenous administrations were similar. Study C indicated that levofloxacin was rapidly and completely absorbed from the oral tablets, with mean times to the maximum concentration of drug in serum of approximately 1.5 h and mean absolute bioavailability of > or =99%. These results support the interchangeability of the oral and intravenous routes of levofloxacin administration.
在两项独立的随机、双盲、平行设计、安慰剂对照研究中，对40名健康男性志愿者进行了每日一次口服左氧氟沙星（研究A）或静脉注射左氧氟沙星（研究B）的药代动力学研究。在第1天，口服或静脉注射500 mg左氧氟沙星或安慰剂作为单剂量给药；在第4至10天恢复每日口服或静脉给药。在第三项研究（研究C）中，在一项开放标签、随机、三向交叉研究中，对24名健康男性受试者研究了两种口服和一种静脉注射左氧氟沙星制剂的生物利用度可比性。在第1天，给予500 mg左氧氟沙星单片或静脉输注；经过1周的洗脱期后，受试者接受第二种给药方案（即另一种口服制剂或静脉输注）；在经过1周的洗脱期后给予第三种也是最后一种给药方案。通过经过验证的高压液相色谱法测量血浆和尿液中的药物浓度。通过非房室方法估算药代动力学参数。在研究A（口服左氧氟沙星）和研究B（静脉注射左氧氟沙星）中，在第4天开始多次给药后的48小时内均达到稳态。对于单次和多次500 mg、每日一次口服和静脉给药方案，左氧氟沙星的药代动力学呈线性且可预测，口服和静脉给药的药代动力学参数值相似。研究C表明，左氧氟沙星从口服片剂中迅速且完全吸收，血清中药物达到最大浓度的平均时间约为1.5小时，平均绝对生物利用度≥99%。这些结果支持左氧氟沙星口服和静脉给药途径的互换性。
