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Related Experiment Videos

Protein binding predictions in infants.

Patrick J McNamara1, Jane Alcorn

  • 1Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA. pmcnamar@uky.edu

AAPS Pharmsci
|June 7, 2002
PubMed
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Drug binding in newborns differs due to lower plasma protein levels. A predictive model accurately estimates drug binding fractions in infants and children based on age-related protein changes.

Area of Science:

  • Pharmacology
  • Neonatal Physiology
  • Drug Metabolism

Background:

  • Plasma protein concentrations, crucial for drug binding, vary significantly between newborns and adults.
  • Human serum albumin (HSA) levels are near adult concentrations at birth, while alpha 1-acid glycoprotein (AAG) levels are substantially lower.
  • This difference impacts how drugs bind, affecting their availability and efficacy in neonates.

Purpose of the Study:

  • To investigate the impact of age-dependent plasma protein concentration changes on drug binding in infants and children.
  • To develop and validate a predictive model for estimating unbound drug fractions in pediatric populations.

Main Methods:

  • Comparison of plasma binding protein concentrations (HSA and AAG) in newborns versus adults.
  • Utilizing a mathematical model incorporating adult unbound fractions and infant-to-adult protein concentration ratios.

Related Experiment Videos

  • Validation of the model's predictions against observed unbound drug fractions in infants and children.

    • Main Results:

    • Newborns exhibit lower plasma binding protein levels compared to adults, which increase with age.
    • Drugs primarily bound to HSA show binding closer to adult levels in newborns, unlike drugs bound to AAG.
    • The developed model successfully predicted the fraction of unbound drugs in infants and children.

    Conclusions:

    • Age-related changes in plasma protein concentrations significantly influence drug binding in pediatric populations.
    • A predictive model utilizing protein concentration ratios can accurately estimate unbound drug fractions in neonates and children.
    • This model aids in optimizing pediatric drug dosing and understanding drug disposition in early life stages.