Hinderling P H, Gundert-Remy U, Förster D, Gau W
J Pharmacokinet Biopharm. 1983 Feb;11(1):5-30. doi: 10.1007/BF01061765.
The pharmacokinetics of the novel acylureidopenicillin furazlocillin, 6-[D-2-(3-furfurylidenamino-2-oxo-imidazolidine-1-carboxamido)-2 -(4-hydroxyphenyl)-acetamido]-penicillanic acid and of its penicilloic acid derivative were investigated in five healthy male volunteers after intravenous administration of 2 and 4 g dosages. The volunteers were either in a lying or sitting position throughout the duration of the studies. The concentrations of the drug in plasma and urine were measured by two different methods in parallel: a microbiological assay and a newly developed high pressure liquid chromatography method. The latter method was also applicable for quantitation of the penicilloic acid derivative in these biological fluids. The drug's plasma protein binding (66%) and apparent red cell-plasma partition coefficient (0.055) were concentration independent. The pharmacokinetics of the drug were first order only at the lower dose level. The apparent half lives of three distinguishable phases were, respectively, 4(t1/21), 18 (t1/22), and 64 (t1/2z) min. The total and renal clearances of the drug were, respectively, 303 and 79 ml/min. The latter value implied tubular secretion of the drug. Graphical and digital computer analyses of the data were performed with a linear three compartment body model. Small but consistent deviations from linear kinetics caused by the nonrenal elimination route were observed after administration of the higher dose (4 g). In contrast, renal elimination showed no such dose dependency and was first order. The disposition kinetics of furazlocillin were body position independent. The penicilloic acid derivative of furazlocillin was found in plasma and urine in all the five subjects tested. The percentage of the dose excreted renally as the derivative amounted, respectively, to 5.2 and 7.0% after the lower and higher dosage of furazlocillin, with significant inter- and intrasubject variability. The renal clearance of the derivative was 41 ml/min.
在5名健康男性志愿者静脉注射2克和4克剂量的新型酰脲基青霉素呋苄西林（6 - [D - 2 -（3 - 糠叉氨基 - 2 - 氧代 - 咪唑烷 - 1 - 甲酰胺基）- 2 -（4 - 羟基苯基）- 乙酰胺基] - 青霉烷酸）及其青霉噻唑酸衍生物后，对它们的药代动力学进行了研究。在整个研究过程中，志愿者均处于卧位或坐位。采用两种不同方法平行测定血浆和尿液中的药物浓度：微生物测定法和新开发的高压液相色谱法。后一种方法也适用于定量这些生物流体中的青霉噻唑酸衍生物。药物的血浆蛋白结合率（66%）和表观红细胞 - 血浆分配系数（0.055）与浓度无关。药物的药代动力学仅在较低剂量水平呈一级动力学。三个可区分阶段的表观半衰期分别为4（t1/21）、18（t1/22）和64（t1/2z）分钟。药物的总清除率和肾清除率分别为303和79毫升/分钟。后一数值表明药物存在肾小管分泌。使用线性三室人体模型对数据进行了图形和数字计算机分析。在给予较高剂量（4克）后，观察到由非肾消除途径导致的与线性动力学的微小但一致的偏差。相比之下，肾消除未显示出这种剂量依赖性，且呈一级动力学。呋苄西林的处置动力学与体位无关。在所有5名受试对象的血浆和尿液中均发现了呋苄西林的青霉噻唑酸衍生物。在较低和较高剂量的呋苄西林给药后，以衍生物形式经肾排泄的剂量百分比分别为5.2%和7.0%，个体间和个体内存在显著差异。衍生物的肾清除率为41毫升/分钟。
