Drug-Drug Interaction Module

This section details the equations that define and support the optional PDPlus™ (DDI) module that Simulations Plus developed for the investigation and prediction of DDIs.

Drug-drug interactions (DDIs) can occur when two or more drugs are co-administered to a patient. DDIs lead to changed systemic exposure, resulting in variations in drug response of the co-administered drugs. Typically, DDIs occur when one drug inhibits the metabolism of another. According to current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidance documents, physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool to explore and quantitatively predict DDIs and it might offer an alternative to dedicated clinical trials.

This section details the optional Drug-Drug Interaction (DDI) module that Simulations Plus developed for the investigation and prediction of DDIs. The module extends the capabilities of GastroPlus® to predict competitive and/or time-dependent drug-drug interactions.

The Metabolism and Transporter module, which is another optionally licensed module developed by Simulations Plus, is required to use the DDI module.

This section covers the following topics:

• DDI Module Overview

• Steady State Calculations with the DDI Module

• Dynamic Simulations with the DDI Module

For details about the internal standards that were used to define the equations in this section, see Equation Standards.