Physiologically-based Pharmacokinetic (PBPK) Modeling

PBPK modeling is used to make predictions of the absorption, distribution and elimination of a compound from an organism. It requires the building of a virtual organism using mathematical functions and realistic information on the organism’s anatomy and physiology. It also requires an understanding of how compound-specific properties such as lipophilicity, molecular weight and acid/base properties affect the way the compound interacts with the organs and tissues of the organism.

PBPK model structure

The model is structured such that the virtual organism is as realistic as possible,

  • Organs have a volume and blood flow
  • Total body weight is equal to the sum of all organ/tissue weights
  • The sum of all blood flows equals the flow through the lung (cardiac output)
  • Compound administration is realistic and can be into the stomach (oral dose), venous blood (intravenous dose), onto the skin (dermal absorption) etc.
  • Organs accumulate compound at a rate and to an extent that is reasonable based on the compound properties
  • Organs of elimination remove compound from the system

Using a very specific workflow, PBPK models can be used to predict the pharmacokinetics of compounds in any organism. We prefer to stick to warm-blooded animals! So what is the difference between a rat and a human or an adult human and a 1 year-old child…anatomy and physiology! So by changing the physiology of our virtual organism, we can simulate the pharmacokinetics in many different kinds of mammals, the most common being humans, monkeys, rats, dogs and mice. This can be helpful in the following ways:

  • Aid is the development of pharmaceuticals where preliminary studies are completed in rats, dogs and monkeys and the first dose given to man needs to be identified
  • Simulation of the expected required pharmaceutical dose in children that gives equal internal exposure as compared to adults
  • In human health risk assessment, determine the potential differential risks of contaminant exposure to adult humans and children based on their varied physiologies

Funding has been provided by

  • Pharma Industry
  • School of Pharmacy, University of Waterloo
  • Ontario Centres of Excellence - VIP I Program
  • Defence Research and Development Canada (Toronto)
  • NSERC Discovery
  • US National Institutes of Health (NIH)