DDI Module Overview

The DDI Module extends the functionality of GastroPlus® by predicting potential metabolic and transporter-based DDIs. The module can account for pure competitive or time-dependent inhibition of a substrate's metabolism, induction of a substrate's metabolism, competitive or time-dependent inhibition of carrier-mediated transport, and induction of carrier-mediated transport. You can using steady-state assumptions to estimate the change in a victim drug’s (substrate) exposure (AUC ratio) that is the result of the presence of a perpetrator (inhibitor and/or inducer), or you can run full dynamic simulations to obtain predictions of concentration versus time profiles for the victim, perpetrator, and any of their metabolites upon co-administration of two or more parent drugs.

The steady-state calculations, which are applicable to metabolic DDI only, automatically incorporate the contribution of gut and liver metabolism to the overall change in exposure of the victim drug (substrate). With these predictions, you have the option to select from several types of perpetrator concentrations to explore their effects on the outcome. You can also perform a “pseudo” steady-state calculation using simulated perpetrator concentrations within the steady-state equation. In this situation, you can explore the effect of the perpetrator on the overall change in the victim's exposure, with the victim administered at different times relative to the perpetrator's dosing (the victim either co-administered with the perpetrator or administered sometime after the perpetrator on different days of the perpetrator's dosing). See Steady State Calculations with the DDI Module.

The dynamic simulations include the effects of altered metabolism and carrier-mediated transport in gut, liver and, with the use of a PBPK model* in any other tissue which might be contributing to the metabolism or where distribution might be dependent on carrier-mediated transport of the victim, perpetrator, and any compound in their respective metabolic pathways. If an enzyme or transporter affects multiple compounds (victim, perpetrator, or their metabolites), then GastroPlus® automatically adjusts for the competition among these compounds for the enzyme/transporter binding sites. See Dynamic Simulations with the DDI Module.

The optionally licensed PBPKPlus™ Module is required.