2013
DOI: 10.1038/psp.2013.55
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Application of Physiologically Based Pharmacokinetic Modeling to Predict Acetaminophen Metabolism and Pharmacokinetics in Children

Abstract: Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that undergoes extensive phase I and II metabolism. To better understand the kinetics of this process and to characterize the dynamic changes in metabolism and pharmacokinetics (PK) between children and adults, we developed a physiologically based PK (PBPK) model for APAP integrating in silico, in vitro, and in vivo PK data into a single model. The model was developed and qualified for adults and subsequently expanded for application in child… Show more

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Cited by 96 publications
(96 citation statements)
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References 49 publications
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“…Such an ontogeny-based approach has been successfully used recently to predict pediatric drug disposition of acetaminophen (Jiang et al, 2013). Together, the CES1 absolute ontogeny data presented here show a difference in the prodrug-metabolizing capacities of neonates and infants versus those of older children and adults.…”
Section: Age-dependent Hepatic Carboxylesterase Abundancementioning
confidence: 77%
“…Such an ontogeny-based approach has been successfully used recently to predict pediatric drug disposition of acetaminophen (Jiang et al, 2013). Together, the CES1 absolute ontogeny data presented here show a difference in the prodrug-metabolizing capacities of neonates and infants versus those of older children and adults.…”
Section: Age-dependent Hepatic Carboxylesterase Abundancementioning
confidence: 77%
“…During the development of the PBPK model, prior knowledge of the biological system is often used to help identify the behavior of drugs in different systems, such as children and patients with decreases in renal function (12,38,39). This PBPK analysis, on the other hand, showcases the potential of using the drug information to help understand the system.…”
Section: Discussionmentioning
confidence: 99%
“…Several groups reviewed the use of PBPK in pediatric drug development and research, with various versions of workflow being proposed to predict drug PK in pediatrics using PBPK (Barrett et al, 2012;Leong et al, 2012;Jiang et al, 2013;Maharaj and Edginton, 2014;Willmann et al, 2014). All proposals articulate the importance of establishing/ verifying an adult PBPK model, followed by utilizing the most up-todate pediatric physiology models to prospectively predict drug PK in subjects of different pediatric age groups.…”
Section: Discussionmentioning
confidence: 99%