Fattinger K, Vozeh S, Olafsson A, Vlcek J, Wenk M, Follath F
Department of Internal Medicine, University Hospital, Basel, Switzerland.
Clin Pharmacol Ther. 1991 Jul;50(1):55-65. doi: 10.1038/clpt.1991.103.
Netilmicin pharmacokinetics were studied in neonates of 27 to 42 weeks' gestational age and 0.8 to 5.0 kg body weight in their first 2 weeks of life by the population pharmacokinetic approach. The data were best described by a two-compartment model. Clearance depends on body weight, gestational age, and postnatal age. Volume of distribution of the central and peripheral compartments was also related to body weight. Including these patient characteristics in the population pharmacokinetic regression model resulted in a marked reduction of the unexplained interindividual variability. This enabled us to derive dosage recommendations that result in peak and average concentrations within the desired range for 95% of the neonates with gestational age above 31 weeks, thus avoiding the need for individual drug-level monitoring in a well-defined large group of patients. Only for infants with gestational age less than 31 weeks who are less than 6 days old is individual dose adjustment based on serum concentration measurements required.
采用群体药代动力学方法，对27至42周胎龄、体重0.8至5.0千克的新生儿出生后前2周的奈替米星药代动力学进行了研究。数据用二室模型能得到最佳描述。清除率取决于体重、胎龄和出生后年龄。中央室和周边室的分布容积也与体重有关。在群体药代动力学回归模型中纳入这些患者特征后，可明显降低个体间无法解释的变异性。这使我们能够得出剂量推荐，对于胎龄大于31周的95%新生儿，可使其峰浓度和平均浓度处于期望范围内，从而避免了在一大群明确界定的患者中进行个体药物水平监测的必要性。仅对于胎龄小于31周且出生不足6天的婴儿，才需要根据血清浓度测量进行个体剂量调整。
