Jaehde U, Sörgel F, Naber K G, Zürcher J, Schunack W
Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany.
Antimicrob Agents Chemother. 1995 Sep;39(9):2092-7. doi: 10.1128/AAC.39.9.2092.
The distribution kinetics of enoxacin and its main metabolite oxoenoxacin in excretory fluids was investigated in 11 healthy volunteers. A single intravenous dose of 428 mg of enoxacin was given as a 1-h infusion. Serial samples of plasma, urine, saliva, nasal secretions, tears, and sweat were drawn and analyzed for enoxacin and oxoenoxacin by reversed-phase high-pressure liquid chromatography. Large differences in the concentration-time profiles of the excretory fluids analyzed were observed. Nasal secretions exhibited the highest enoxacin exposure, as assessed by the area under the concentration-time curve. Excretory fluid/plasma area under the concentration-time curve ratios were found to be 1.67 +/- 0.36 for nasal secretions, 0.76 +/- 0.28 for saliva, 0.25 +/- 0.07 for sweat, and 0.23 +/- 0.11 for tears. The elimination half-life of enoxacin from sweat (8.27 +/- 2.63 h) was significantly longer than that for plasma (5.10 +/- 0.46 h). Oxoenoxacin was detected in urine and saliva and exhibited a higher renal clearance and a lower saliva exposure than the parent compound. In contrast to that of the metabolite, distribution of enoxacin in saliva was found to be time and pH dependent. In conclusion, our study revealed considerable differences in the distribution kinetics of enoxacin among various excretory sites. Because of distinct acidic and basic properties, the anionic oxometabolite significantly differs from the zwitterionic parent compound in its distribution characteristics.
在11名健康志愿者中研究了依诺沙星及其主要代谢产物氧氟沙星在排泄液中的分布动力学。以1小时静脉输注的方式给予428mg依诺沙星单次静脉剂量。采集血浆、尿液、唾液、鼻分泌物、泪液和汗液的系列样本，并用反相高效液相色谱法分析其中的依诺沙星和氧氟沙星。观察到所分析的排泄液的浓度-时间曲线存在很大差异。通过浓度-时间曲线下面积评估，鼻分泌物中依诺沙星的暴露量最高。发现排泄液/血浆浓度-时间曲线下面积比，鼻分泌物为1.67±0.36，唾液为0.76±0.28，汗液为0.25±0.07，泪液为0.23±0.11。依诺沙星在汗液中的消除半衰期（8.27±2.63小时）明显长于血浆中的消除半衰期（5.10±0.46小时）。在尿液和唾液中检测到氧氟沙星，其肾清除率高于母体化合物，在唾液中的暴露量低于母体化合物。与代谢产物不同，发现依诺沙星在唾液中的分布与时间和pH值有关。总之，我们的研究揭示了依诺沙星在不同排泄部位的分布动力学存在显著差异。由于具有不同的酸性和碱性性质，阴离子型氧代谢产物在分布特征上与两性离子型母体化合物有显著差异。
