Pharmacokinetics of Muscle Relaxants in Children
Several studies in the early 1980’s improved our understanding of relationship of the physiologic changes with maturation to the pharmacokinetics of three nondepolarizing muscle relaxants, d-tubocurarine (dTc) (1), vecuronium (2), and atracurium (3). Because these muscle relaxants are polar, water-soluble molecules, their distribution should be limited to the extracellular fluid space (ECF). In fact, volume of distribution at steady state (Vss) of the three drugs correlates with ECF; its values are of the same order of magnitude as ECF (20–40% of body weight) and age-related changes parallel those of ECF. A second finding was that the neuromuscular junction of the neonate was sensitive (as defined by a lower steady state plasma concentration, Css, producing paralysis), consistent with the electromyographic findings of decreased prejunctional acetylcholine stores observed in neonates and infants (4,5).
KeywordsMuscle Relaxant Interindividual Variability Plasma Cholinesterase Plasma Cholinesterase Activity Nondepolarizing Muscle Relaxant
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- 9.Caldwell JE, Szenohradszky J, Segredo V, et al.: The pharmacodynamics and pharmacokinetics of the metabolite 3-desacetylvecuronium (ORG 7268) and its parent compound, vecuronium, in human volunteers. J Pharmacol Exp Ther, in pressGoogle Scholar
- 11.Hashimoto Y, Sheiner LB: Designs for population pharmacodynamics: Value of pharmacokinetic data and population analysis. J Pharmacokin Biopharmaceut 19:333–353, 1991Google Scholar
- 12.Vuksanaj D, Dunbar B, Skjonsby B, Fisher DM: Neuromuscular effects and pharmacokinetics of rocuronium in children aged 4–12 years. SubmittedGoogle Scholar