New Features/Changes
GastroPlus™ 7.0
1.
Drug-Drug Interaction Module (NEW):
o
Prediction of metabolic drug-drug interactions
o
Steady-state predictions as well as full dynamic simulations
o
Competitive and time-dependent inhibition
o
Interactions among parent compounds and any of their metabolites
o
Database of ready-to-use models (Compartmental PK and PBPK) for a number of substrates and inhibitors commonly used in clinical DDI studies
2.
Additional Dosage Routes Module (NEW):
o
Drug absorption after inhaled administration
o
Drug absorption after ocular administration
o
Drug uptake into the eye from systemic circulation
3.
Metabolism and Transporter Module additions:
o
Tracking of metabolites formed in gut
o
Tracking of metabolites formed in liver with Compartmental PK
o
Tracking of metabolites formed in any tissue with PBPK
o
Formation of multiple metabolites from one parent compound
o
Formation of metabolites of metabolites
4.
ADMET Predictor™ Module additions:
o
Predict solubilities in simulated gastric fluid (FaSSGF) and simulated intestinal fluids (FaSSIF and FeSSIF)
5.
Number of minor bug fixes and changes to increase usability
New Features/Changes
GastroPlus™ 6.1
1.
Solubility and dissolution modeling:
o
Mechanistic effect of bile salts on drug dissolution in vivo
o
Enhanced treatment of nano-particle dissolution
o Expanded selection of dissolution models (Johnson (Default), Wang-Flanagan, or Sugano)
2.
IVIVCPlus™ Module capabilities are expanded:
o
A Numerical Deconvolution method in now available
o
Ability to graph multiple plots after IVIVC and Convolution
o
Automatic fitting of multiple correlation functions and selection of the best model
o
In vivo release can be modeled using a single- or double-Weibull function
3.
PBPKPlus™ Module improvements include:
o
Automatic scaling of adult physiologies based on different body weights
o
Ability to create a user-defined physiology (specify tissue weights as % of body weight and tissue perfusions as % of cardiac output)
o
Automatic scaling of enzyme expression levels in liver and gut to pediatric populations based on age
o
Calculation of Adjusted Fup is now based on logD (rather than logP) to account for drug ionization in plasma (NOTE: This may cause a difference in your simulations if enzymes were included in your model)
4.
ADMET Predictor™ Module additions:
o
Predict blood:plasma concentration ratio (Rbp) from structure
o
The structure will now be displayed upon import
o New structure-specific logD calculation
5.
Metabolism and Transporter Module options:
o
Ability to include basolateral enterocyte transporters in simulation
o
Obtain in vivo clearance parameters (CLint or Km & Vmax) from in vitro measurements in recombinant systems (rCYP)
o
Fixed FPE can be specified separately for oral cavity, gut and liver
6.
New dosage forms for drug delivery to oral cavity:
o
Sublingual tablet
o
Lingual spray
o
Buccal patch (controlled-release)
7.
New General Units Converter tool
8.
Number of enhancemants and new convenience features
New Features/Changes
GastroPlus™ 6.0
1. Complete upgrade to our IVIVCPlus™ Module:
• Novel mechanistic deconvolution method to determine the actual in vivo dissolution of
your formulation
• Classical deconvolution methods (Wagner-Nelson and Loo-Riegelman) incorporated
• Choice of three functional forms (linear, power, polynomial) for correlation equations
• Easy convolution setup to predict Cp-time profiles for new in vitro curves
• Deconvolution and correlation function fitting across multiple data sets
• Ability to save and reload deconvolution/correlation results
2. Expansion to the PKPlus™ capabilities:
• Now fit compartmental PK models to both iv and oral Cp-time data
• Fitting of compartmental models across multiple data sets (iv, oral, combination of iv and oral,
combination of different dose levels)
• Ability to fit F% (if fitting to a combination of iv and oral data), average ka, and lag-time to
oral Cp-time data
• Improved plotting features
3. Improvements to PBPKPlus™:
• New method for the calculation of fraction unbound in tissues
• Enhanced kidney model (mechanistic description of renal secretion, reabsorption, and clearance)
• Interface changes that simplify the use of PBPK models
4. Redesigned PDPlus™ Module with improved plotting capabilities
5. Metabolite tracking is now available for metabolism occurring in PBPK tissues (this feature requires the licensing of the PBPKPlus and Metabolism and Transporter modules)
6. 3D Parameter Sensitivity Analysis feature to explore the simultaneous effect of two parameters on
Fa%, F%, Cmax, Tmax and AUC
7. Save custom formats for single simulation, PDPlus, and PKPlus plots (saves the most common
formatting changes like font sizes, types and colors of chart titles, axis titles and axis labels)
8. Resizable windows
9. Updated model for logD-pH calculation
New Features/Changes
GastroPlus™5.3
1. ADMET Predictor Module - create a database from a structure file (.MOL, .SDF, .RDF, etc.) and get instant predictions of physico-chemical properties.
2. Cross-over Virtual Trials
3. New integrator for faster simulations
4. New dosage forms: Enteric Coated Capsule and Enteric Coated Tablet
5. Redesigned Metabolism and Transporter Units Converter for a more intuitive and user friendly interface
6. Shape factor in particle size distribution to simulate the dissolution of cylindrical particles
7. Monkey PBPK model
8. Convenience features:- Save Simulation Time in database
- A list of recently accessed databases
- Extended Batch mode output:
New Features/Changes
GastroPlus™5.2
1. Ability to run Virtual Trials and Parameter Sensitivity Analysis with respect to Pharmacodynamic response
2. Added Biliary clearance option to Liver tissue in PBPK models including the ability to use saturable transport of drug from hepatocytes to bile
3. Added Rodgers & Rowland method of tissue:plasma partition coefficient calculation
4. A number of convenience features:
- fit Solubility-pKa model to users' solubility-pH profile for smoother interpolation and more accurate extrapolation of experimental solubility data
- fit Weibull function to discrete dissolution/release-time profile for smoother interpolation and easier optimization of in vivo dissolution/release profile
- fit particle size distribution to discrete data as well as cumulative distribution
- utility for setting up Mixed Multiple dose support files
- ability to fit parameters to defined therapeutic window for fixed multi-dose regimen
- ability to load back Virtual Trial and PSA results for easier sharing of results with colleagues
New Features/Changes
GastroPlus™5.1
1. Particle size distribution was added to the dissolution model. Users can now select from two built-in distributions (Normal and Log-Normal) or create their own distribution of particle sizes.
2. The default log D absorption model has been re-calibrated with more compounds for which the experimental human jejunal permeability values and observed fraction absorbed became available. This modification might cause differences in absorption profiles for some compounds. Please contact us if you need any help matching previous results using the new models.
3. The volumes of individual gut compartments are now being calculated from lengths and radii and can no longer be modified directly.
4. The geometrical parameters of individual compartments and transit times are now automatically scaled to subject weight to reflect the differences between adult and pediatric populations when body weight is < 77.5 kg.
5. Upon request of some users, we have added an option of going back to the ACAT models and treatment of precipitation time as they were implemented in version 4. Even though we do not recommend building new models with these outdated settings, it might be helpful in matching the results obtained by version 4 and version 5.
6. The functions of the Metabolism and Transporter Units converter have been greatly extended and it is now more closely connected with the Enzyme and Transporter tables as well as facilitating the calculation of intrinsic clearance from a variety of user - supplied units or from just half-life data.
7. More flexibility has been added to the calculation of Tissue:Plasma partition coefficients (only applicable for PBPK models). Users can now select from two methods for each, perfusion - and permeability - limited tissues.
8. Optimization against individual tissue concentrations in PBPK models is now available with adjustable objective function weights for each component.
9. The saving options for Batch mode and Parameter sensitivity analysis have been extended. Both simulation modes can now save also Cp-time profiles for individual simulations.
New Features/Changes
GastroPlus™5.0
1. We have now completed the physiologically-based pharmacokinetic module. This is a major addition to GastroPlus and we strongly advise you to go through the GastroPlus manual before using this new module.
2. Human-fasted and Human-fed physiologies have been modified to reflect more accurate geometries and volumes for the colon. Users who have built models with the previous default equal transit time models may see some difference in the dissolution profiles of poorly soluble drugs using the new models. The Human Physiological Fasted and Fed models combined with the log D absorption model are now the default models
3. Handling of the user-supplied precipitation time has been modified. Users may find slightly different dissolution profiles with their existing database setting for low solubility weak bases that previously precipitated when reaching the small intestine.
4. Plotting of graphs has been greatly enhanced and all oral and iv plasma concentration vs. time files will accept a coefficient of variation (CV% for each time point).
5. The virtual trial is now able to generate Population Estimates for Age-Related Physiology if the PBPK module is unlocked. The virtual trial plots now contain error bars, bioequivalence limits, 90% confidence intervals, and probability lines from 10% - 100%.
6. Both Parameter Sensitivity Analysis and the Optimization Module have been expanded to include more parameters.
7. Greater flexibility is provided for objective function weighting during optimization.