Stoeckel K
Chemotherapy. 1981;27 Suppl 1:42-6. doi: 10.1159/000238028.
The total (bound and unbound) plasma concentration time profiles following the three intravenous doses of Rocephin (150, 500 and 1,500 mg) declined in a biphasic manner. A simple compartment analysis was inappropriate since a dose-disproportional increase in the area under the total drug concentration time curve (AUCT,0(-8)) occurred. This resulted in unstable, dose-dependent total systemic clearance (9.7-13.0 ml/min) and volume of distribution (7.0-8.6 litres) values. The dose-dependent pharmacokinetic changes could be completely explained in terms of the concentration-dependent plasma protein binding (fp ranging from 0.04 to 0.17 in the concentration range from 0.5 to 300 micrograms/ml). Hence, the pharmacokinetics of free (unbound) Rocephin was linear and dose-independent. With reference to free (unbound) drug the mean total clearance was 255 ml/min and the mean renal clearance about 160 ml/min. The renal clearance was therewith slightly higher than the average glomerular filtration rate in man (approximately 125 ml/min). Consequently the coadministration of probenecid (1 g) had no effect on the pharmacokinetics of Rocephin. The mean plasma half-life of Rocephin was not influenced by dose and averaged 8 h. It was therewith the longest ever reported one for a cephalosporin in healthy volunteers.
静脉注射三次罗氏芬（150、500和1500毫克）后的总（结合和未结合）血浆浓度-时间曲线呈双相下降。由于总药物浓度-时间曲线下面积（AUCT,0(-8)）出现剂量不成比例增加，简单房室分析并不合适。这导致总全身清除率（9.7 - 13.0毫升/分钟）和分布容积（7.0 - 8.6升）值不稳定且依赖于剂量。剂量依赖性药代动力学变化可以完全用浓度依赖性血浆蛋白结合来解释（在0.5至300微克/毫升浓度范围内，fp范围为0.04至0.17）。因此，游离（未结合）罗氏芬的药代动力学呈线性且与剂量无关。以游离（未结合）药物计算，平均总清除率为255毫升/分钟，平均肾清除率约为160毫升/分钟。肾清除率略高于人类平均肾小球滤过率（约125毫升/分钟）。因此，丙磺舒（1克）的合用对罗氏芬的药代动力学没有影响。罗氏芬的平均血浆半衰期不受剂量影响，平均为8小时。这是健康志愿者中报道的头孢菌素最长的半衰期。
