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

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Computational Biology
• Drug Development

Background:

• Physiologically based pharmacokinetic (PBPK) models offer realistic simulations of drug behavior.
• Existing PBPK models are often solute-specific, parameter-intensive, and lack general applicability.

Purpose of the Study:

• To introduce PKQuest, a novel, general-purpose PBPK software.
• To provide an easy-to-use, physiologically rigorous tool for pharmacokinetic analysis.

Main Methods:

• PKQuest features "Standardhuman" and "Standardrat" datasets to minimize user input.
• Includes advanced features like solving for absorption, permeability limitations, saturable protein binding, lung models, and optimization routines.
• Offers a general non-linear system solver for drug absorption and systemic availability.

Main Results:

• PKQuest successfully modeled human propranolol pharmacokinetics and intestinal absorption.
• Demonstrated meal effects on portal blood flow and liver metabolism.
• Observed delayed oral propranolol absorption in fasting versus fed subjects, with extended absorption for long-acting formulations.

Conclusions:

• PKQuest is a versatile, accessible, and physiologically sound PBPK software.
• It is freely available at www.pkquest.com for broad scientific use.