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Pharmacokinetics and pharmacodynamics of atracurium in infants and children
D M Fisher1, P C Canfell, M J Spellman
1Department of Anesthesia, University of California, San Francisco 94143-0648.
Insights
Atracurium pharmacokinetics and pharmacodynamics in infants, children, and adults show age-related changes in distribution and clearance. However, elimination half-life and sensitivity to atracurium remain consistent across age groups.
Area of Science:
- Pharmacology
- Anesthesiology
- Pediatric Medicine
Background:
- Maturational changes in body composition and organ function may influence drug pharmacokinetics and pharmacodynamics.
- Understanding these changes is crucial for optimizing drug administration in pediatric populations.
Purpose of the Study:
- To investigate the impact of maturational changes on the pharmacokinetics and pharmacodynamics of atracurium.
- To compare atracurium's distribution, elimination, and sensitivity in infants, children, and adults.
Main Methods:
- Pharmacokinetic and pharmacodynamic analyses of atracurium in infants, children, and adults.
- Atracurium infusion followed by measurement of adductor pollicis muscle twitch tension.
- Plasma sample analysis using liquid chromatography and pharmacokinetic modeling.
Main Results:
- Volume of distribution and total clearance of atracurium decreased with increasing age.
- Elimination half-life and the plasma concentration required for 50% neuromuscular blockade did not significantly vary with age.
- These findings suggest age-related differences in atracurium distribution and elimination but not in its neuromuscular effects.
Conclusions:
- Maturational changes affect atracurium's distribution and clearance, with larger volumes and higher clearance in younger individuals.
- Atracurium's elimination half-life and sensitivity are not significantly influenced by age.
- The results explain why recovery from atracurium's neuromuscular effects is minimally affected by age.
Abstract:
To determine whether maturational changes in body composition and organ function affect distribution and elimination of and sensitivity to atracurium, the authors determined the pharmacokinetics and pharmacodynamics of atracurium in six infants and five children and compared these results with those obtained in five adults. Atracurium, 15.8 +/- 1.7 micrograms.kg-1.min-1, was infused iv for 6-11 min to subjects anesthetized with nitrous oxide (60%) and halothane (0.9 MAC, age-adjusted) and twitch tension of the adductor pollicis muscle was measured. Plasma samples were obtained for 120 min; concentrations of atracurium were determined using a liquid chromatographic assay. A two-compartment pharmacokinetic model, adapted to account for elimination of atracurium from both central and peripheral compartments, was fit to the plasma concentration data; an effect-compartment model was fit to the twitch tension data. Volume of distribution at steady state (210 +/- 118, 129 +/- 44, and 100 +/- 22 ml/kg for infants, children, and adults, respectively) and total clearance (7.9 +/- 2.0, 6.8 +/- 1.6, and 5.3 +/- 0.9 ml.kg-1.min-1 for the three groups) decreased with increasing age. Neither elimination half-life (20.0 +/- 5.1, 17.2 +/- 5.1, and 15.7 +/- 2.5 min for the three groups) nor the steady state plasma concentration that resulted in 50% neuromuscular blockade (363 +/- 118, 444 +/- 121, and 436 +/- 122 ng/ml for the three groups) varied with age. The authors conclude that these results are consistent with and explain the previously reported findings that recovery from the neuromuscular effects of atracurium is minimally affected by age.(ABSTRACT TRUNCATED AT 250 WORDS)