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Related Experiment Videos

Neonatal phenobarbital and phenytoin binding profiles

M J Painter1, M B Minnigh, L Gaus

  • 1Department of Pediatrics, University of Pittsburgh, Pennsylvania.

Journal of Clinical Pharmacology
|April 1, 1994
PubMed
Summary

Neonatal drug binding for phenobarbital and phenytoin is lower than in adults, influenced by protein levels, birth weight, and gestational age. In vitro binding accurately predicts in vivo drug levels in newborns.

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Area of Science:

  • Pharmacology
  • Neonatal Medicine
  • Drug Metabolism

Background:

  • Phenobarbital and phenytoin are commonly used anticonvulsants.
  • Neonatal drug disposition differs significantly from adults due to physiological immaturity.
  • Understanding drug binding is crucial for optimizing neonatal therapy.

Purpose of the Study:

  • To determine the binding profiles of phenobarbital and phenytoin in neonates.
  • To investigate factors influencing drug binding in this population.
  • To assess the predictive value of in vitro binding for in vivo drug concentrations.

Main Methods:

  • Drug binding assays were performed on 27 neonates.
  • In vitro binding was correlated with total protein and albumin levels.

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  • In vivo binding was assessed at 0.5 hours and correlated with clinical parameters.
  • The influence of concomitant medications, bilirubin, free fatty acids, and pH was evaluated.

    • Main Results:

    • Both phenobarbital and phenytoin showed decreased binding in neonates compared to older subjects.
    • In vitro binding correlated significantly with total protein and albumin.
    • In vivo binding correlated with birth weight and gestational age.
    • Phenobarbital binding decreased with co-administration of other drugs, but phenytoin did not.
    • Bilirubin, free fatty acids, and pH did not significantly affect binding.
    • In vitro binding accurately predicted in vivo free fractions and plasma concentrations.

    Conclusions:

    • Neonatal drug binding is reduced and influenced by specific factors like protein and gestational age.
    • In vitro binding assays are reliable predictors of in vivo drug behavior in neonates.
    • These findings aid in optimizing phenobarbital and phenytoin dosing in newborns.