Mechanistic Modeling of In Vitro Biopharmaceutic Data for a Weak Acid Drug: A Pathway Towards Deriving Fundamental Parameters for Physiologically Based Biopharmaceutic Modeling

The objective of this tutorial is to (1) review processes and parameters contributing to oral drug absorption in increasing levels of complexity, (2) outline a general physiologically based biopharmaceutic modeling workflow for weak acids, and (3) illustrate the outlined concepts via an ibuprofen (i.e., a weak, poorly soluble acid) case example in order to provide practical guidance on how to integrate biopharmaceutic and physiological data to better understand oral drug absorption. In the future, we plan to explore the usefulness of this tutorial/roadmap to inform the development of PBPK models for BCS 2 weak bases, by expanding the stepwise modeling approach to accommodate more intricate scenarios, including the presence of diprotic basic compounds and acidifying agents within the formulation.Graphical Abstract
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research