Preface

Welcome to the GastroPlus® Equations Guide. The collection of mathematical models and equations that are used in GastroPlus® simulate the effects of a variety of physicochemical, physiological, and formulation parameters on the absorption, distribution, and elimination (metabolism and excretion) of drugs after administration via a variety of dosage routes, and with the appropriate pharmacokinetic inputs, the plasma and tissue concentration profiles for both human and animal species. The purpose of the GastroPlus® Scientific Principles Guide is to provide basic, but thorough, descriptions of these mathematical models and equations, which, in turn, helps you understand how to use GastroPlus® efficiently and effectively.

Guide layout

The GastroPlus® Scientific Principles Guide has a dual purpose design. It can be distributed electronically and then printed on an as-needed basis, or it can be viewed online in its fully interactive capacity. If you print the document, for best results, it is recommended that you print it on a duplex printer; however, single-sided printing also works.

Conventions used in the guide

The GastroPlus® Scientific Principles Guide uses the following conventions:

Units are not provided for any of the equations in this guide. To view the units for the inputs to an equation, refer to the GastroPlus® software.
Where appropriate, for consistency of presentation and to facilitate the understanding of the scientific principles detailed in this guide, the symbols/letters used to represent variables in many equations have been changed from those referenced in the literature to the symbols /letters that adhere to Simulations Plus’s internal documentation standards for GastroPlus®. To view the original symbol/letter for a variable, refer to the appropriate referenced manuscript.
Because you can view this guide online, then if information appears in blue, it is a hyperlink. Click the hyperlink to advance to the referenced information.

Organization of the guide

To facilitate comprehension of the mathematical models and equations that are detailed in this guide, the information is organized based on the pharmacokinetics principles of absorption, distribution, and elimination (metabolism and excretion). Additional chapters and appendices address related topics, including pharmacodynamics, drug-drug interactions, in vitro and in vivo correlations, and virtual bioequivalence.

In addition to this Preface, the GastroPlus® Scientific Principles Guide contains the following chapters and appendices:

ACAT Model Equations details the equations that define and support the Advanced Compartmental Absorption and Transit (ACAT) model developed by Simulations Plus, which extends the capabilities of the pre-cursor Compartmental Absorption and Transit (CAT) model to include in vivo drug behavior of first-pass metabolism and colonic absorption.
Pharmacokinetics Equations details the equations that define and support the optional PBPKPlus™ module that Simulations Plus developed for the simulation of physiologically-based pharmacokinetics (PBPK) of drug candidates.
Pharmacodynamics Equations details the equations that define and support the optional PDPlus™ model that Simulations Plus developed for modeling multiple PD effects for any drug record in a database.
Drug-Drug Interaction Module Equations details the equations that define and support the optional Drug-Drug Interaction (DDI) module that Simulations Plus developed for the investigation and prediction of DDIs.
In Vitro and In Vivo Correlation Plus Module Equations details the equations that define and support a Level A IVIVC, which is a specific category of IVIVC that you can carry out in the optional In Vitro and In Vivo Correlation Plus (IVIVCPlus™) module. The IVIVCPlus™ module was developed by Simulations Plus for
carrying out different types of IVIVC correlations.
The Population Simulator Mode and Virtual Bioequivalence Equations details the equations that define and support the Population Simulator feature in GastroPlus®, which you can use to simulate populations in the Virtual Bioequivalence (VBE) run mode to conduct VBE trials.
Additional Dosage Routes Equations details the equations that define and support the Additional Dosage Routes features in GastroPlus®.
Equation Standards details the internal documentation standards that were used to define many of the equations in the GastroPlus® Scientific Principles Guide.