Sjögren, E.; Tarning, J.; Barnes, K.I.; Jonsson, E.N. A Physiologically-Based Pharmacokinetic Framework for Prediction of Drug Exposure in Malnourished Children. Pharmaceutics2021, 13, 204.
Sjögren, E.; Tarning, J.; Barnes, K.I.; Jonsson, E.N. A Physiologically-Based Pharmacokinetic Framework for Prediction of Drug Exposure in Malnourished Children. Pharmaceutics 2021, 13, 204.
Sjögren, E.; Tarning, J.; Barnes, K.I.; Jonsson, E.N. A Physiologically-Based Pharmacokinetic Framework for Prediction of Drug Exposure in Malnourished Children. Pharmaceutics2021, 13, 204.
Sjögren, E.; Tarning, J.; Barnes, K.I.; Jonsson, E.N. A Physiologically-Based Pharmacokinetic Framework for Prediction of Drug Exposure in Malnourished Children. Pharmaceutics 2021, 13, 204.
Abstract
Malnutrition in children is a global health problem, particularly in developing countries. The effects of an insufficient supply of nutrients on body composition and physiological functions may have implications for drug disposition and ultimately affect the clinical outcome in this vulnerable population. Physiologically based pharmacokinetic (PBPK) modeling can be used to predict the effect of malnutrition as it links physiological changes to pharmacokinetic (PK) consequences. However, the absence of detailed information on body composition and the limited availability of controlled clinical trials in malnourished children complicates the establishment and evaluation of a generic PBPK model in this population. In this manuscript we describe the creation of physiologically-based bridge to a malnourished pediatric population, by combining information on a) the differences in body composition between healthy and malnourished adults and b) the differences in physiology between healthy adults and children. Model performance was confirmed using clinical reference data. This study presents a physiologically-based translational framework for prediction of drug disposition in malnourished children. The model is readily applicable for dose recommendation strategies to address the urgent medicinal needs of this vulnerable population.
Keywords
malnutrition; translation; physiologically based pharmacokinetics; PBPK; pediatrics
Subject
Medicine and Pharmacology, Immunology and Allergy
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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