Ganzinger U, Kleinberger G, Lenz K, Schatz F, Laggner A, Grimm G
Int J Clin Pharmacol Ther Toxicol. 1987 Jul;25(7):354-62.
The pharmacokinetics of ceftazidime and netilmicin were evaluated under septicemic conditions. In a longitudinal study, both drugs were administered simultaneously (ceftazidime 2.0 g 20 min constant i.v. infusion and netilmicin 150 mg i.v. bolus injection) every 12 hours to patients who had a positive blood culture and hyperdynamic circulatory functions. Twenty-four hours after the first period of this pharmacokinetic study, identical parameters were evaluated under dipyrone induced normothermic conditions. The mean residence time and the volume of distribution was significantly altered during septicemia compared to normal conditions. With respect to the relative distribution properties ceftazidime tended to be distributed to a greater extent to the tissue compartment, whereas netilmicin showed an opposite behaviour. Beside significant correlations of absolute values, i.e. blood volume vs. volume of distribution, and relative values, i.e. total peripheral resistance vs. extraction rate, all other attempts failed to show any meaningful correlation. Owing to the heterogenous alterations of metabolic and hemodynamic functions and pharmacokinetic parameters, respectively, the data gained from this study do not allow any statistically validated conclusion regarding the pathophysiological mechanisms involved, although these findings are in accordance with animal experiments.
在败血症条件下评估了头孢他啶和奈替米星的药代动力学。在一项纵向研究中，对血培养呈阳性且循环功能亢进的患者每12小时同时给予两种药物（头孢他啶2.0 g静脉恒速输注20分钟，奈替米星150 mg静脉推注）。在该药代动力学研究的第一个阶段24小时后，在安乃近诱导的正常体温条件下评估相同的参数。与正常情况相比，败血症期间平均驻留时间和分布容积有显著改变。就相对分布特性而言，头孢他啶倾向于在更大程度上分布到组织隔室，而奈替米星则表现出相反的行为。除了绝对值（即血容量与分布容积）和相对值（即总外周阻力与提取率）之间存在显著相关性外，其他所有尝试均未显示出任何有意义的相关性。由于代谢和血流动力学功能以及药代动力学参数分别存在异质性改变，尽管这些发现与动物实验一致，但本研究获得的数据不允许就所涉及的病理生理机制得出任何经统计学验证的结论。
