Vuksanaj D, Fisher D M
Department of Anesthesiology, Baylor College of Medicine, Texas Children's Hospital, Houston, USA.
Anesthesiology. 1995 May;82(5):1104-10. doi: 10.1097/00000542-199505000-00003.
Rocuronium is a new nondepolarizing muscle relaxant with a rapid onset and intermediate duration of action. Although the pharmacokinetics of rocuronium have been determined in adults and the elderly, similar data are lacking in children. Accordingly, rocuronium's pharmacokinetics were determined in children aged 4-11 yr.
Rocuronium (600 micrograms/kg) was administered to 20 children aged 4-11 yr anesthetized with nitrous oxide and < or = 1% halothane, and four plasma samples were obtained over 4 h to determine rocuronium concentrations. The pharmacokinetics of rocuronium were determined using two sparse-sampling population approaches, mixed-effects modeling, and naive pooled data analysis.
With mixed-effects modeling, weight-normalized plasma clearance varied with weight (P < 0.01), being 79.4 ml.min-1 + 3.13 ml.kg-1.min-1. Neither weight-normalized distributional clearance (2.67 ml.kg-1.min-1), weight-normalized central compartment volume (106 ml/kg), nor weight-normalized volume of distribution at steady-state (224 ml/kg) varied with weight, height, or age. Similar results were obtained with the naive pooled data approach.
Maturational changes were observed in rocuronium's weight-normalized clearance but not in its weight-normalized distributional clearance or volume of distribution. Assuming that the duration of rocuronium's neuromuscular effects is influenced by its pharmacokinetics, repeated administration or continuous infusion of rocuronium should result in larger dose requirements and more rapid recovery in younger, compared to older, children.
罗库溴铵是一种新型非去极化肌松药，起效迅速，作用时间中等。虽然罗库溴铵的药代动力学已在成人和老年人中得到确定，但儿童中缺乏类似数据。因此，对4至11岁儿童的罗库溴铵药代动力学进行了测定。
对20名4至11岁、用氧化亚氮和≤1%氟烷麻醉的儿童给予罗库溴铵（600微克/千克），并在4小时内采集4份血浆样本以测定罗库溴铵浓度。使用两种稀疏采样群体方法、混合效应建模和单纯合并数据分析来确定罗库溴铵的药代动力学。
采用混合效应建模时，体重标准化血浆清除率随体重变化（P<0.01），为79.4毫升·分钟-1 + 3.13毫升·千克-1·分钟-1。体重标准化分布清除率（2.67毫升·千克-1·分钟-1）、体重标准化中央室容积（106毫升/千克）或稳态时体重标准化分布容积（224毫升/千克）均不随体重、身高或年龄变化。采用单纯合并数据方法也得到了类似结果。
观察到罗库溴铵的体重标准化清除率有成熟变化，但其体重标准化分布清除率或分布容积没有变化。假设罗库溴铵的神经肌肉效应持续时间受其药代动力学影响，与年长儿童相比，年幼儿童重复给药或持续输注罗库溴铵应导致更大的剂量需求和更快的恢复。
