D Vuksanaj1, D M Fisher. 1. Department of Anesthesiology, Baylor College of Medicine, Texas Children's Hospital, Houston, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.