Chulavatnatol S, Chindavijak B, Vibhagool A, Wananukul W, Sriapha C, Sirisangtragul C
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
J Med Assoc Thai. 1999 Nov;82(11):1127-35.
The pharmacokinetics of levofloxacin, a new fluoroquinolone, were investigated in 12 healthy Thai male volunteers with an average age (SD) of 22.92 (2.50) years. A single oral dose of 300 mg or 500 mg levofloxacin was given to subjects following an 8- hour overnight fast. The drug was given in a controlled, randomized, 2 x 2 crossover design with a 1 week washout period. Venous blood samples were drawn prior to and from 0.25 up to 48 hours after dosing. Plasma levofloxacin concentrations were determined by HPLC assay. The pharmacokinetics of levofloxacin were well described by a linear, 2-compartment open model with first-order absorption with lag time and first-order elimination. Mean +/- SEM of Cmax after 300 mg and 500 mg dose was 4.83 +/- 0.33 and 7.75 +/- 0.71 micrograms/mL, respectively. Tmax ranged from 0.7 to 0.8 hours for both doses. Mean +/- SEM of AUC0-infinity was 35.77 +/- 2.06 micrograms x h/mL for 300 mg dose and 61.57 +/- 2.84 micrograms x h/mL for 500 mg dose. High distribution with VSS/F value of approximately 1.5 L/kg was demonstrated after both doses. Mean +/- SEM of CL/F value was 8.64 +/- 0.41 L/h and 8.31 +/- 0.37 L/h for a 300-mg and a 500-mg dose, respectively. Long t1/2 beta of 7 to 8 hours with the mean residence time of 10.43 +/- 0.43 hours and 10.49 +/- 0.38 hours after 300 mg and 500 mg dose, respectively, was observed. The results suggested that an oral 300 mg dose once daily provides sufficient Cmax to cover most Gram-negative and atypical bacteria (median MIC90 0.032-0.5 microgram/mL) common in mild to moderate respiratory tract infections or complicated urinary tract infections and Gram-positive bacteria (median MIC90 0.5 microgram/mL) common in skin and soft tissue infections. For severe cases or Streptococcus pneumoniae (MIC90 2 micrograms/mL) infection, a 500-mg dose should be recommended.
在12名健康的泰国男性志愿者中研究了新型氟喹诺酮类药物左氧氟沙星的药代动力学，这些志愿者的平均年龄（标准差）为22.92（2.50）岁。在禁食过夜8小时后，给受试者单次口服300mg或500mg左氧氟沙星。药物以对照、随机、2×2交叉设计给药，洗脱期为1周。在给药前以及给药后0.25小时至48小时采集静脉血样。通过高效液相色谱法测定血浆左氧氟沙星浓度。左氧氟沙星的药代动力学通过具有滞后时间的一级吸收和一级消除的线性二室开放模型得到很好的描述。300mg和500mg剂量后的Cmax均值±标准误分别为4.83±0.33和7.75±0.71μg/mL。两种剂量的Tmax均在0.7至0.8小时之间。300mg剂量的AUC0-∞均值±标准误为35.77±2.06μg·h/mL，500mg剂量的为61.57±2.84μg·h/mL。两种剂量给药后均显示出较高的分布，VSS/F值约为1.5L/kg。300mg和500mg剂量的CL/F值均值±标准误分别为8.64±0.41L/h和8.31±0.37L/h。观察到300mg和500mg剂量后的t1/2β较长，分别为7至8小时，平均驻留时间分别为10.43±0.43小时和10.49±0.38小时。结果表明，每日一次口服300mg剂量可提供足够的Cmax，以覆盖轻度至中度呼吸道感染或复杂性尿路感染中常见的大多数革兰氏阴性菌和非典型细菌（MIC90中位数为0.032 - 0.5μg/mL）以及皮肤和软组织感染中常见的革兰氏阳性菌（MIC90中位数为0.5μg/mL）。对于严重病例或肺炎链球菌（MIC90为2μg/mL）感染，应推荐500mg剂量。
