Joos B, Ledergerber B, Flepp M, Bettex J D, Lüthy R, Siegenthaler W
Antimicrob Agents Chemother. 1985 Mar;27(3):353-6. doi: 10.1128/AAC.27.3.353.
Ciprofloxacin was given orally to 10 healthy volunteers for seven consecutive doses of 250 mg every 12 h. Serum and urine samples were collected at distinct times between 0 and 96 h and analyzed both by high-pressure liquid chromatography and by a microbiological assay. The detection limits were 0.006 and 0.03 microgram/ml, respectively. For each method, imprecision coefficients of variation were less than 6.1% at various concentrations in serum and urine. The means +/- standard deviations of the absolute values of the relative differences between the two methods were 9.3 +/- 6.8% (n = 225) for serum samples and 58.5 +/- 50.4% (n = 70) for urine samples. Comparison of the concentrations in serum measured with high-pressure liquid chromatography and bioassay by regression analysis yielded a slope which was not significantly different from 1.0 (99.9% confidence limits: 0.984 less than slope less than 1.035). In urine, however, the bioassay results were markedly higher than the high-pressure liquid chromatography values (1.327 less than slope less than 1.698), which indicates the presence of antimicrobially active metabolites. The cumulative 12-h urinary recovery after the first and seventh doses averaged 30.2 +/- 8.5 and 26.4 +/- 4.6%, respectively, by high-pressure liquid chromatography, whereas with bioassay 38.2 +/- 5.9 and 45.5 +/- 5.9% activity was recovered. Protein binding appeared to be neither concentration nor pH dependent and averaged 21.9 +/- 4.1%.
给10名健康志愿者口服环丙沙星，每12小时连续给药7次，每次250毫克。在0至96小时的不同时间采集血清和尿液样本，并用高压液相色谱法和微生物测定法进行分析。检测限分别为0.006和0.03微克/毫升。对于每种方法，血清和尿液中不同浓度下的不精密度变异系数均小于6.1%。两种方法相对差异绝对值的均值±标准差，血清样本为9.3±6.8%（n = 225），尿液样本为58.5±50.4%（n = 70）。通过回归分析比较高压液相色谱法和生物测定法测得的血清浓度，得到的斜率与1.0无显著差异（99.9%置信限：0.984＜斜率＜1.035）。然而，在尿液中，生物测定结果明显高于高压液相色谱法的值（1.327＜斜率＜1.698），这表明存在具有抗菌活性的代谢物。首次和第七次给药后12小时的累积尿回收率，高压液相色谱法平均分别为30.2±8.5%和26.4±4.6%，而生物测定法回收的活性分别为38.2±5.9%和45.5±5.9%。蛋白质结合似乎既不依赖于浓度也不依赖于pH值，平均为21.9±4.1%。
