| FAQ
|
|
|
Simulations Plus FAQ Section
Please select the product you are interested in by using the pull down menu on the left.
|
| Question: Our company has GastroPlus with multiple licenses installed on a server. Other users can run GastroPlus, but when I start it, I get a message that the license is expired or the number of users has been exceeded. What should I do? |
Answer: Check with your IT department and find out if you have the correct privileges to the directory where the license file is placed on the server. Every user must have full (read/write/destroy/modify) access to the license file in order to run GastroPlus. If that does not fix the problem, contact Simulations Plus, Inc.
|
| Question: How do I add data, for example, experimental plasma concentration data, to a plot? |
Answer: These data need to be placed in an OPD (for oral doses) or IPD (for IV doses) support file. GastroPlus loads these files at the start of the simulation and automatically displays the experimental points on the plot along with the simulated curve. The files can be created through menus “File/Load/6 Load Oral Plasma Conc vs Time Data” for OPD file and “File/Load/5 Load Intravenous Plasma Conc vs Time Data” for IPD file.
|
| Question: I have created an OPD file with my experimental plasma concentration data, but the points are not showing on the plot. What should I do? |
Answer:
The support files are recognized by GastroPlus only if (1) they are placed in the same directory as the current database and (2) their name matches exactly the name of the current record. If these two conditions are met, the file will be listed in the drug information window in the upper right corner of the Compound tab. If the file is not listed there, GastroPlus was not able to find it. Make sure that the file has the correct name and is in the correct location.
|
| Question: Can I use GastroPlus to predict the variability in a pharmacokinetic (PK) response? |
Answer:
Yes! The Virtual Trial feature in GastroPlus allows
you to predict the variability in a PK and/or pharmacodynamic (PD) profile for
the parent compound and its metabolite(s). You may also simulate the
variability in PK/PD responses for a selected population (American or Japanese,
specified gender ratio, specified age range) or set of formulation parameters
(e.g., particle size, dose).
|
| Question: Can I use GastroPlus to predict the PK response in a pediatric population? |
Answer:
Yes! The PEAR
Physiology (Population Estimates for Age Related Physiology) feature
in GastroPlus includes scaling of physiological parameters to a pediatric
population. This feature allows you to quickly create the physiology for a
child of a defined age and gender. You can also run Virtual Trials to estimate
the variability in PK/PD responses in specific pediatric populations.
|
| Question: I would like to run simulations for a specific disease state or a physiology affected by prior administration of certain drug (e.g., elevated stomach pH). What can I do? |
Answer: GastroPlus comes with a set of default gut and
full body (PBPK) physiological parameters for healthy subjects. However, all
parameters in these physiologies can be adjusted to the condition you would
like to simulate. As long as you know what parameters are affected by the
specific condition (e.g., elevated stomach pH, increased fat content, decreased
renal function), you can adjust the physiological parameters and save this
user-defined physiology for use in your simulations.
|
| Question: Can I use GastroPlus to predict the PK response from in vitro or pre-clinical data? |
Answer:
Of course! The Metabolism and Transporter module
in GastroPlus includes a convenient units converter for IVIVE (in vitro – in vivo extrapolation). The
animal gut and PBPK physiologies provided in GastroPlus allow you to run
simulations for pre-clinical species, figure out the mechanism of the drug’s interactions
in the body, and properly scale to human based on known differences between
physiologies.
|
| Question: My drug is undergoing enterohepatic circulation. Can I simulate the effects of meals on the plasma concentration-time profile? |
Answer:
Yes! GastroPlus includes a model for biliary
secretion and enterohepatic circulation. You also have the ability to
administer meals at specific times (through our Mixed Multiple Dosing feature),
resulting in the emptying of gallbladder and reabsorption of the fraction of
drug that was cleared through biliary secretion.
|
| Question: How can GastroPlus help me with formulation design? |
Answer: The Parameter Sensitivity Analysis feature
allows you to quickly examine the effects of formulation parameters (e.g.,
particle size, particle shape) on the absorption or PK/PD response. With the
optional Optimization module, you can determine the optimum in vivo release profile to achieve the
desired plasma concentration-time profile or to keep steady-state plasma
concentration within a therapeutic window. The new IVIVCPlus module allows you
to quickly and easily establish an in
vitro-in vivo correlation (IVIVC).
This
refers to finding the relationship between how a dosage form dissolves in the
lab (in vitro) with how it dissolves in human or animals (in vivo).
The understanding of these differences helps scientists in several ways: (1)
designing the ideal formulation faster and with fewer experiments, (2)
designing an in vitro experiment that is a better representation of in
vivo release, and (3) getting better estimates of blood concentration-time
profiles for similar new formulations prior to full-blown clinical trials.
|
| Question: I would like to use GastroPlus to simulate gastrointestinal absorption but I don’t know all input parameters. Is there anything I can do? |
Answer:
Of course! GastroPlus includes an optional ADMET
Predictor module which can help you generate in silico estimates for the required inputs. It uses the same
models as our first-in-class ADMET PredictorTM program to predict a
compound’s biopharmaceutical properties (e.g., logP, solubility, permeability,
pKa, plasma protein binding, and volume of distribution in human) from
structure. These in silico estimates
are a good starting point for initial simulations. Using the Parameter
Sensitivity Analysis feature, you can begin to identify the critical parameters
governing your compound’s dissolution and absorption along the GI tract and
help focus your resources on in vitro
experiments covering those properties that really matter.
|
| Question: Can I use the permeability measured in a cell-based assay (Caco2, MDCK, etc…) as an input to GastroPlus? |
Answer:
GastroPlus includes a Peff converter tool that
allows you to create the correlation between the Papp values
measured in your in vitro assay and
human jejunal permeability (Peff). Peff values are
included in GastroPlus, so all you need to do is to supply your Papp
measurements for a set of standard compounds. Within the converter tool, you
can create and export the correlation generated, which will then become
available to you within GastroPlus for automatic conversions of Papp
to Peff.
|
|
|
|