01. Discover
What is the PBPKPlus™ Module?

Ranked as the #1 PBPK software for In Vitro-In Vivo Extrapolation (IVIVE) & PBPK modeling by Pfizer! (Cole et al., 2nd Asian Pacific Regional ISSX Meeting, May 2008, Shanghai, China)

03. About
About PBPKPlus™ Module

The PBPKPlus™ Module extends GastroPlus™ to define a physiologically based pharmacokinetic (PBPK) model consisting of various tissues. You can easily simulate the distribution and elimination of compound throughout the body and track concentrations in any tissue. Any tissue can employ fixed intrinsic clearance and with the Metabolism and Transporter Module, saturable (Michaelis-Menten) metabolism and transport (influx and efflux) can be incorporated. Tissues can be defined as needed, or default models can be used with a standard set of compartments:

  • Adipose
  • Arterial blood
  • Brain
  • Gut
  • Heart
  • Lungs
  • Liver
  • Muscle
  • Skin
  • Spleen
  • Reproductive organs
  • Venous blood
  • Kidney
  • Yellow marrow
  • Red marrow

Customize your PBPK model by treating any tissue as either a perfusion-limited or permeability-limited model, and quickly add/delete tissues as needed – all without writing any equations using the GastroPlus PBPK software!

NEW! Transporter-based IVIVE: automated scaling of permeability across tissues using a single parameter! Check out the Resource Center for more details on the approach and how it can be applied to scale across species or populations!

Transporter based IVIVE PBPK model

  • Generation of physiological model parameters (tissue weights and volumes, perfusion rates, etc…) with our built-in PEAR Physiology™ (Population Estimates for Age-Related Physiology). Current physiology models are:
  • Human (American or Asian, male or female, healthy, liver disease, obesity, renal impairment – based on age)
  • Infant/pediatric groups
  • Rat
  • Dog
  • Mouse
  • Monkey
  • Rabbit
  • Minipig

A screenshot of the GastroPlus PEAR Physiology™ portion shows PEAR Inputs and Outputs for a human, with options to specify species, heart rate, weight, and more; outputs display crucial organ data such as the Hepatic Artery and Lung for pharmacodynamics studies, along with a reminder about adipose tissue.

  • Run population PBPK simulations (through the Population Simulator™) based on parameter variances in a sample population. Generate up to 2500 subjects in a single, Monte Carlo-based run, or reuse existing populations to perform virtual crossover studies. Define your own age & BMI range, % male vs. female, and the number of “virtual” subjects you wish to create
  • Updated! Covariates for gastrointestinal physiology and age/gender of virtual PBPK subjects created
  • Novel methods for estimating tissue partition coefficients in PBPK models from logD, pKa, plasma protein binding, and Rbp – only GastroPlus has the upgraded “Rodgers-Rowland” (Lukacova) method, developed in collaboration with Roche
  • Physiological models for kidney, including glomerular filtration and reabsorption
  • Parameter Sensitivity Analysis of nearly all physiological, physicochemical, pharmacokinetic, and metabolism/transporter parameters
  • Fit models to in vivo data in single or multiple compartments (Optimization Module required) – use plasma/tissue concentrations, amount excreted in urine, etc…
  • Link pharmacodynamic effect directly to drug concentration in specific tissues (PDPlus™ Module required)
  • Mechanistic transport of drug from hepatocytes to bile in liver, modeled either as a linear process or through carrier-mediated transport (Metabolism and Transporter Module required)
  • Report-quality plotted output of all time-dependent results in all tissues in your PBPK models – can be captured through any simulation run (Parameter Sensitivity Analysis, Batch, or Population Simulator)

A plot generated using Simulations Plus' GastroPlus software illustrates the pharmacodynamics of terbinafine concentrations in rats over 24 hours, with the x-axis representing simulation time in hours (0-24h) and the y-axis showing concentration in mg/mL (1E-5 to 1E3), including four different data series with corresponding legends and recorded results on the graph.

04. Resources
PBPKPlus™ Resources

Want to incorporate PBPK modeling to inform regulatory interactions?