GastroPlus™

PBPK modeling software – from discovery through
development…

Choose a Module:

Drug Drug Interaction

What is the DDI Module?

The DDI Module in GastroPlus™ allows you to predict mechanistic and static drug-drug interactions (DDIs) among drugs and metabolites. The ability to accurately estimate potential DDIs in silico has several benefits for pharmaceutical companies:

  • Explore possible effects on the pharmacology and toxicology of drugs
  • Identify species-specific changes to estimate how a drug behaves in animals vs. humans
  • Investigate the safety profile of drugs that are co-administered prior to filing regulatory submissions with the FDA, EMA, and other agencies

Resources

With the DDI Module, calculating either mechanistic steady-state and/or dynamic drug interactions is managed through our easy-to-use interface. We provide a database of standard compounds for which all relevant parameters (including reported Kis and full compartmental PK/PBPK models) are defined. Of course, you may predict DDIs among any drugs by simply entering the required inputs. As with other GastroPlus modules, there is no equation or code writing required.

What are some of the advantages to using the GastroPlus DDI Module?

NEW! Population Simulator™ linked with DDI predictions! Now incorporate variability between subjects in your dynamic simulations and see the impact on victim, perpetrator, and metabolite(s) concentrations and AUC ratios. Define your population (American, Asian, pediatric, etc…) and number of subjects (up to 2500) in your trial to start.

  • Once the simulations are completed, view the mean results and 90% confidence intervals for the concentration-time profiles and major endpoints (e.g., Cmax, AUC)

What else can we do with the GastroPlus DDI Module?

  • Transporter-based drug-drug interactions
  • Metabolic and/or transporter induction
  • Linked with the industry’s #1-ranked dissolution/absorption (ACAT™) model
  • Use with either 1-, 2-, or 3-compartment PK models or physiologically based pharmacokinetic models (PBPKPlus™)
  • Apply competitive and/or time-dependent inhibition kinetics by parent and/or metabolite(s)
  • Simulate DDIs for any species (human, beagle, rat, mouse, rhesus monkey, cymonologous monkey, minipig, rabbit, or cat)
  • Account for enzyme expression level differences in various populations (Caucasian and Asian)
  • Built-in tool to calculate the fraction metabolized (fm) from in vitro assays (rCYPs and microsomes are accommodated)
  • Incorporate nonlinear gut contributions to DDIs
  • Predict the inhibitor effect using simulated concentrations at the site of metabolism (gut, liver, or any PBPK tissue) for dynamic DDI simulations
  • Include the effects of multiple substrates on clearance of other substrates metabolized by the same enzyme