Sörgel F, Seelmann R, Naber K, Metz R, Muth P
Department of Pediatrics, University of Essen, Federal Republic of Germany.
J Antimicrob Chemother. 1988 Oct;22 Suppl D:169-78. doi: 10.1093/jac/22.supplement_d.169.
The metabolism of fleroxacin was studied in 12 healthy volunteers by use of a newly developed high pressure liquid chromatographic assay. Desmethylfleroxacin and fleroxacin N-oxide were identified as the major metabolites of fleroxacin in plasma and urine. The maximum concentrations of fleroxacin, desmethylfleroxacin and fleroxacin N-oxide in plasma were 5.2 +/- 1.1, 0.0683 +/- 0.0151 and 0.0634 +/- 0.0090 mg/l reached at 1.2 +/- 0.7 h, 2.2 +/- 0.8 h and 6.2 +/- 2.4 h respectively (one subject excluded from analysis). The plasma AUC was between 1.0 and 2.6 mg.h/l for either metabolite and between 47.9 and 75.1 mg.h/l for the parent compound. The terminal half-life of desmethylfleroxacin was higher than that of unchanged fleroxacin and similar to the half-life of fleroxacin N-oxide. In urine unchanged fleroxacin, desmethylfleroxacin and fleroxacin N-oxide accounted for 59.9%, 6.8% and 6.3% of the dose of fleroxacin. The renal clearance of fleroxacin, desmethylfleroxacin and fleroxacin N-oxide were 67.6, 300.9 and 324.8 ml/min respectively. We conclude that demethylation and N-oxidation of fleroxacin affects the distribution and elimination characteristics significantly. Renal clearance increased, and it is suggested that the volume of distribution may increase also.
采用新开发的高压液相色谱分析法，在12名健康志愿者身上研究了氟罗沙星的代谢情况。去甲基氟罗沙星和氟罗沙星N - 氧化物被鉴定为血浆和尿液中氟罗沙星的主要代谢产物。血浆中氟罗沙星、去甲基氟罗沙星和氟罗沙星N - 氧化物的最大浓度分别为5.2±1.1、0.0683±0.0151和0.0634±0.0090mg/L，分别在1.2±0.7小时、2.2±0.8小时和6.2±2.4小时达到（一名受试者被排除在分析之外）。两种代谢产物的血浆曲线下面积（AUC）在1.0至2.6mg·h/L之间，母体化合物的血浆AUC在47.9至75.1mg·h/L之间。去甲基氟罗沙星的终末半衰期高于未变化的氟罗沙星，与氟罗沙星N - 氧化物的半衰期相似。在尿液中，未变化的氟罗沙星、去甲基氟罗沙星和氟罗沙星N - 氧化物分别占氟罗沙星剂量的59.9%、6.8%和6.3%。氟罗沙星、去甲基氟罗沙星和氟罗沙星N - 氧化物的肾清除率分别为67.6、300.9和324.8ml/min。我们得出结论，氟罗沙星的去甲基化和N - 氧化显著影响其分布和消除特征。肾清除率增加，并且提示分布容积可能也增加。
