Extrapolation of acetaminophen PK models from adults to paediatricians

Extrapolation of PK models from adults to paediatricians requires re-qualification of physiological and pharmacokinetic parameters. Specifically, maturation of metabolism pathways, urinary clearance and rapid weight changes in paediatricians affect PK profiles. In this presentation we describe a case study of extrapolating a clinical acetaminophen (APAP) PK model from adults to neonates (<28 days) and infants (29 days – 1 year). The PK model consists of two compartments (blood and urine) with Michaelis-Menton equations describing the glucuronidation, sulfation and oxidation reactions, and linear functions for recovery of metabolites in urine. The parameters used in the validated adult PK model are re-assessed in the paediatric PK model using a Latin hypercube method. Furthermore, a virtual population trial on 200 subjects are run using the Monte-Carlo method. The model is then qualified against published in vivo, in vitro and in silico studies of APAP PK. Such a model practice, after validated with clinical data, could provide a useful computational workflow as the first step in PK model extrapolation from adults to paediatricians. 

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  • University of Auckland, New Zealand
Dr Ho received PhD in Bioengineering from the University of Auckland in 2011. His research interests include mathematical modelling for physiological flows, physiologically based pharmacokinetics modelling, 3D visualisation of bio-structures, medical image computing and surgical simulations. He is the first or corresponding author of ~40 peer-reviewed international journal papers/book chapters, including the top journals in his research field.