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Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children

Frederique Rodieux1, Melanie Wilbaux2, Johannes N van den Anker3,4,5

  • 1Department of Pediatric Clinical Pharmacology, Pediatric Pharmacology and Pharmacometrics Research Center, University Children's Hospital (UKBB), University of Basel, Spitalstrasse 33, CH-4056, Basel, Switzerland. Frederique.Rodieux@ukbb.ch.

Clinical Pharmacokinetics
|July 4, 2015
PubMed

Insights

Pediatric drug dosing requires careful consideration of kidney function changes during growth. Novel biomarkers and pharmacometric modeling can optimize medication for children, especially those with impaired renal function.

Area of Science:

  • Pharmacology
  • Pediatrics
  • Nephrology

Background:

  • Pediatric patients exhibit unique physiological differences from adults, impacting drug pharmacokinetics and response.
  • Current pediatric drug dosing often relies on adult data adjusted for body size, potentially leading to suboptimal therapeutic outcomes or adverse events.
  • Kidney function undergoes significant changes during early childhood, influencing drug absorption, distribution, metabolism, and clearance.

Purpose of the Study:

  • To highlight the impact of developmental changes in kidney function on drug disposition in pediatric populations.
  • To explore the utility of 'omics'-based technologies and pharmacometric modeling in optimizing pediatric drug dosing.
  • To present a case study on amikacin dosing in neonates with impaired kidney function.

Main Methods:

  • Leveraging 'omics'-based technologies (proteomics, metabolomics) to identify novel renal function biomarkers.
  • Applying pharmacometric modeling and simulation to analyze drug exposure-response relationships in children.
  • Conducting a case study on amikacin dosing in neonates with reduced kidney function.

Main Results:

  • Developmental changes in kidney function significantly affect drug pharmacokinetics in neonates, infants, and children.
  • 'Omics' technologies offer potential for identifying new biomarkers of kidney function in pediatric populations.
  • Pharmacometric modeling can aid in refining pediatric dosing strategies, particularly for those with renal impairment.

Conclusions:

  • Optimizing pediatric drug dosing necessitates a comprehensive understanding of evolving kidney function and individual patient variability.
  • Integrated approaches combining novel biomarkers, pharmacometric modeling, and collaborative data sharing are crucial for improving drug safety and efficacy in children.
  • Enhanced drug labeling and standardized dosing strategies are needed for medications used in pediatric patients, especially neonates.

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