Dagrosa E E, Hajdú P, Malerczyk V, de Looze S, Seeger K, Grötsch H
Clinical Research Department, Hoechst Aktiengesellschaft, Frankfurt am Main, Federal Republic of Germany.
Clin Ther. 1987;10(1):18-31.
Pharmacokinetics of cefodizime, a broad-spectrum cephalosporin antibiotic, were determined after intravenous (IV) administration of single doses of 1.0, 1.5, and 2.0 gm to 12 healthy male volunteers in an open study. In a separate pilot study, data were obtained after IV administration of 0.5 gm of cefodizime to six healthy male volunteers. Determinations of cefodizime in serum and urine using a microbiological assay agreed with determinations using high-pressure liquid chromatography (HPLC), which specifically measures the unchanged drug. Active metabolites of cefodizime were not detected. After IV administration of 1.0, 1.5, and 2.0 gm of cefodizime, initial mean serum concentrations were 215, 322, and 394 mg/L, respectively (HPLC determinations). A linear response to dosage was shown (coefficient of correlation r = .89), as was the case for area under the serum concentration-time curve to infinity, AUC infinity (r = .82), and 48-hour urinary recovery of cefodizime (r = .94). In all cases, the corresponding values obtained after the 0.5-gm dose showed that the linearity extended to this dose. The kinetics of single-dose administration of cefodizime corresponded to a two-compartment open model with an apparent steady-state volume of distribution of about 40 L. Volume of distribution, terminal elimination half-life, serum and renal clearance, and percent urinary recovery were not dose dependent. Cefodizime combined a long terminal elimination half-life (mean, 2.5 hours) with a high urinary recovery (80%). After IV administration of cefodizime, urinary concentrations of the unchanged drug remained above 5 micrograms/ml for at least 24 hours after drug administration and were dose dependent. Mean values for the 1.0-gm and 2.0-gm doses were, respectively, approximately 12 mg/L and 30 mg/L, several times the minimal inhibitory concentrations (MIC90) for most clinically relevant bacteria. These results suggest that once- or twice-daily IV dosing with cefodizime (depending on the dose regimen) would be suitable for clinical use. The drug was safe and well tolerated.
在一项开放性研究中，对12名健康男性志愿者静脉注射单剂量1.0克、1.5克和2.0克的广谱头孢菌素抗生素头孢地嗪，测定其药代动力学。在另一项预试验研究中，对6名健康男性志愿者静脉注射0.5克头孢地嗪后获取数据。使用微生物测定法测定血清和尿液中的头孢地嗪，结果与使用高压液相色谱法（HPLC）的测定结果一致，HPLC专门测量未变化的药物。未检测到头孢地嗪的活性代谢物。静脉注射1.0克、1.5克和2.0克头孢地嗪后，初始平均血清浓度分别为215毫克/升、322毫克/升和394毫克/升（HPLC测定）。显示出对剂量的线性反应（相关系数r = 0.89），血清浓度-时间曲线下面积至无穷大（AUC infinity）（r = 0.82）以及头孢地嗪48小时尿回收率（r = 0.94）也是如此。在所有情况下，0.5克剂量后获得的相应值表明线性延伸至该剂量。头孢地嗪单剂量给药的动力学符合二室开放模型，表观稳态分布容积约为40升。分布容积、终末消除半衰期、血清和肾脏清除率以及尿回收率百分比均与剂量无关。头孢地嗪具有长的终末消除半衰期（平均2.5小时）和高的尿回收率（80%）。静脉注射头孢地嗪后，给药后至少24小时内未变化药物的尿浓度保持在5微克/毫升以上，且与剂量有关。1.0克和2.0克剂量的平均值分别约为12毫克/升和30毫克/升，是大多数临床相关细菌最小抑菌浓度（MIC90）的几倍。这些结果表明，根据剂量方案，每日一次或两次静脉注射头孢地嗪适用于临床使用。该药物安全且耐受性良好。
