Physiologically-Based Pharmacokinetic (PBPK) Modeling and Risk Assessment

2011 ◽  
pp. 536-570 ◽  
Author(s):  
H.J. Clewell ◽  
R.A. Clewell ◽  
M.E. Andersen
Keyword(s):  
Risk Assessment ◽  
Pbpk Modeling ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

The use of in vitro metabolic parameters and physiologically based pharmacokinetic (PBPK) modeling to explore the risk assessment of trichloroethylene

2002 ◽  
Vol 11 (3-4) ◽  
pp. 259-271 ◽  
Author(s):  
Erna M. Hissink ◽  
Jan J.P. Bogaards ◽  
Andreas P. Freidig ◽  
Jan N.M. Commandeur ◽  
Nico P.E. Vermeulen ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Metabolic Parameters ◽  
Pbpk Modeling ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

scholarly journals Reconstructing Organophosphorus Pesticide Doses Using the Reversed Dosimetry Approach in a Simple Physiologically-Based Pharmacokinetic Model

2012 ◽  
Vol 2012 ◽  
pp. 1-8
Author(s):  
Chensheng Lu ◽  
Leo Andres
Keyword(s):  
Risk Assessment ◽  
Pharmacokinetic Model ◽  
Pbpk Model ◽  
Organophosphorus Pesticide ◽  
Pbpk Modeling ◽  
Physiologically Based Pharmacokinetic Model ◽  
Urinary Biomarker ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based ◽  
Composite Data

We illustrated the development of a simple pharmacokinetic (SPK) model aiming to estimate the absorbed chlorpyrifos doses using urinary biomarker data, 3,5,6-trichlorpyridinol as the model input. The effectiveness of the SPK model in the pesticide risk assessment was evaluated by comparing dose estimates using different urinary composite data. The dose estimates resulting from the first morning voids appeared to be lower than but not significantly different to those using before bedtime, lunch or dinner voids. We found similar trend for dose estimates using three different urinary composite data. However, the dose estimates using the SPK model for individual children were significantly higher than those from the conventional physiologically based pharmacokinetic (PBPK) modeling using aggregate environmental measurements of chlorpyrifos as the model inputs. The use of urinary data in the SPK model intuitively provided a plausible alternative to the conventional PBPK model in reconstructing the absorbed chlorpyrifos dose.

scholarly journals A Physiologically-Based Pharmacokinetic Framework for Prediction of Drug Exposure in Malnourished Children

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 204
Author(s):  
Erik Sjögren ◽  
Joel Tarning ◽  
Karen I. Barnes ◽  
E. Niclas Jonsson
Keyword(s):  
Body Composition ◽  
Drug Exposure ◽  
Drug Disposition ◽  
Pediatric Population ◽  
Model Performance ◽  
Vulnerable Population ◽  
Pbpk Modeling ◽  
Malnourished Children ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

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.

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