Pharmacokinetics of ceftazidime and netilmicin in patients with sepsis

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.