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A Physiologically Based Pharmacokinetic Model to Describe Artemether Pharmacokinetics in Adult and Pediatric Patients

Wen Lin1, Tycho Heimbach1, Jay Prakash Jain2

  • 1Drug Metabolism & Pharmacokinetics, Novartis Institutes for Biomedical Research, East Hanover, New Jersey 07936.

Journal of Pharmaceutical Sciences
|August 11, 2016
PubMed

Insights

Artemether exposure is higher in infants under 3 months and weighing less than 5 kg. Physiologically based pharmacokinetic (PBPK) models confirm this finding, aiding malaria treatment optimization.

Area of Science:

  • Pharmacokinetics
  • Pediatric Pharmacology
  • Malaria Treatment

Background:

  • Artemether-lumefantrine is a key malaria treatment for adults and children.
  • Infants show variable artemether exposure, with higher levels in younger, lighter infants.
  • Lumefantrine exposure remains consistent across pediatric age groups.

Purpose of the Study:

  • To characterize artemether exposure in pediatric populations using PBPK modeling.
  • To simulate artemether pharmacokinetics across diverse pediatric age and weight groups.
  • To validate PBPK model predictions against clinical data.

Main Methods:

  • Development of a physiologically based pharmacokinetic (PBPK) model for artemether.
  • Incorporation of artemether physicochemical, biopharmaceutic, and metabolic properties.
  • Model verification with adult clinical data and simulation of pediatric populations (1 month to 12 years).

Main Results:

  • PBPK model simulations accurately reflected observed clinical artemether exposure data.
  • Simulations confirmed higher artemether exposure in infants aged 1-3 months and weighing <5 kg.
  • The PBPK model demonstrated reliability in describing artemether pharmacokinetics in both adults and children.

Conclusions:

  • Physiologically based pharmacokinetic (PBPK) modeling is a robust tool for understanding pediatric drug exposure.
  • The developed PBPK model accurately predicts higher artemether exposure in low-weight, young infants.
  • Findings support optimized dosing strategies for artemether-lumefantrine in pediatric malaria patients.

Keywords:
CYP enzymesclinical pharmacokineticsdrug metabolizing enzymeseliminationhepatic clearanceinterspecies scalingphysiologically based pharmacokinetic modelingpreclinical pharmacokineticssimulations

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