PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol

Background A "physiologically based pharmacokinetic" (PBPK) approach uses a realistic model of the animal to describe the pharmacokinetics. Previous PBPKs have been designed for specific solutes, required specification of a large number of parameters and have not been designed for general use. Methods This new PBPK program (PKQuest) includes a "Standardhuman" and "Standardrat" data set so that the user input is minimized. It has a simple user interface, graphical output and many new features: 1) An option that uses the measured plasma concentrations to solve for the time course of the gastrointestinal, intramuscular, intraperotineal or skin absorption and systemic availability of a drug – for a general non-linear system. 2) Capillary permeability limitation defined in terms of the permeability-surface area products. 4) Saturable plasma and tissue protein binding. 5) A lung model that includes perfusion-ventilation mismatch. 6) A general optimization routine using either a global (simulated annealing) or local (Powell) minimization applicable to all model parameters. Results PKQuest was applied to measurements of human propranolol pharmacokinetics and intestinal absorption. A meal has two effects: 1) increases portal blood flow by 50%; and 2) decreases liver metabolism by 20%. There is a significant delay in the oval propranolol absorption in fasting subjects that is absent in fed subjects. The oral absorption of the long acting form of propranolol continues for a period of more than 24 hours. Conclusions PKQuest provides a new general purpose, easy to use, freely distributed and physiologically rigorous PBPK software routine.

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    "title": "Official Government Data Source",
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    "downloadURL": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC126244/"
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                                            [
  "nih",
  "pbpk-modeling",
  "pharmacokinetics",
  "physiological-modeling",
  "propranolol"
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                                            {
  "name": "National Institutes of Health",
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                                            [
  "NIH"
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