PK-Sim® and MoBi® Releases

All new software releases starting with Open Systems Pharmacology Suite 7.0 can be found at Open Systems Pharmacology.

 

 

Historical Releases

Release Notes for the Systems Biology Software Suite 6.3

 

New features

PK-Sim and MoBi

  • Calculation of time profile confidence intervals as output of parameter identification. Three different types of confidence intervals are supported:

    • Confidence Interval: Corresponds to the model error, which is based on the uncertainty of estimated parameters. This uncertainty is based on an estimation of the difference between the mean value of used observed data compared with the mean value of the (unknown) total data.


             

    • Visual Predictive Check Interval: Corresponds to the uncertainty based on the data error. The data error is the standard deviation of the distribution of the used observed data.

              
             

    • Prediction Interval: Corresponds to the combination of the model error and the data error. It shows how much future measured data are expected to differ from the model predictions.

             
              

  • Sensitivity of PK-Parameters (AUC, CMax, …) vs. simulation parameters.
    Because PBPK models can be complex and contain numerous input parameters, it would be useful to know which input parameters have the most impact on the output curves. The Sensitivity Analysis tool provides an answer to this question.
    For a chosen simulation, the relative impact of selected - or all - input parameters on the PK parameters of the output curves is calculated and displayed. In addition, the input parameters can be ranked by their impact on a certain PK parameter of an output. Results of Sensitivity Analysis can be shown as:

    • Sensitivity table:

             

    • Ranking of most sensitive simulation parameters. Most sensitive parameters comprise all parameters that contribute to 90% of total sensitivity.

                       
             

 

Fixed issues and Improvements

PK-Sim and MoBi

  • 46-7335 Graphical display of Parameter Identification results should match log/lin selection
  • 47-8156 Default Visual Feedback Height little bit to small
  • 46-7325 Only log plots in Parameter Identification
  • 47-8190 Parameter Identification: Weights should all be >=0
  • 47-8185 Covariance matrix and Correlation Matrix should only be calculated for residuals with weight >0
  • 46-7339 Applying default templates to PI charts always hides the Simulation column in data browser
  • 46-7332 Parameter Identification aborted - "Do you really want to import the identified parameters?" shows only "OK"
  • 47-8196 NaN in observed data should be ignored in Parameter Identification
  • 47-8173 Crash showing Covariance/Correlation matrix after removing identification parameters
  • 47-8176 PI Analysis charts: After rerun of Parameter Identification Chart settings/options are reset to default
  • 47-8312 PI Analysis charts: Concentration outputs not shown in mass units

PK-Sim

  • 47-7496 Enable output of concentration/amount in feces
  • 47-8227 Error exporting PK parameter table from comparison plot of individual simulations
  • 47-8148 Population Simulation Time Profile figures sometimes show too many observed data sets
  • 47-8079 Observed data "Amount in Urine/Feces" cannot be mapped to observers
  • 47-6533 "Plasma protein scale factor" is not variable in a population
  • 47-8199 “Export PK-Analysis” missing in ribbon for export of population simulation
  • 47-8195 PI finishes but PK-Sim does not notice that project has changed when closing
  • 47-8287 Specific binding reaction uses wrong concentration if fraction unbound defined in compound is <1

MoBi

  • 46-7319 Using Ctrl/C on an empty parameter list crashes MoBi
  • 46-7323 Re-creating (or deleting) simulation produces error in Parameter Identification
  • 46-7328 Simulation Diagram is messed up after update from Building Block
  • 46-7260 After Update of Building Block in Simulation from Building Blocks Symbols remain partly red
  • 46-7333 Change of "GFR Fraction" in Simulation not committable to Passive Transports Building Block

MoBi Toolbox for Matlab

  • 26-5517 Unicode problems in SaveSimulationToXML
  • 26-5516 Error in getPKParametersForConcentration when calculating Vd or Vss for multiple individuals
  • 26-5503 XML file is saved encrypted
  • 47-8296 Ontogenies cannot be set in MoBi Toolbox for Matlab

 

Known issues

  • If a simulation created in PK-Sim version before 6.1.1 containing a Hepatic or Biliary Plasma Clearance is cloned, the new simulation results may differ from the original one. This is due to the way in which the specific clearance is calculated from the plasma clearances. Intrinsic clearances are calculated from plasma clearances using the well stirred model. These intrinsic clearances are then transformed to specific clearances, which are the internal metric for clearance in PK-Sim. In PK-Sim 6.1, the method used to transform the intrinsic to specific clearance was slightly altered when using plasma clearances.
  • Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.
  • Cloning simulations in projects saved with PK-Sim version before 5.4.1 may reset some non-formula parameters to default value (#47-6141).

 

 

 

 

Release Notes for the Systems Biology Software Suite 6.2

New features

PK-Sim and MoBi

Parameter Identification (PI) fully integrated into both PK-Sim and MoBi (detailed description in Chapter 34 of the Computational Biology Software Suite Manual 6.2).

This allows:

Simultaneous optimization of multiple simulations

Simultaneous optimization of multiple observed data sets

Weights for datasets and single data points

LLOQ (Lower Limit of Quantification) values are taken into account (Ch. 34.7.1)

Linking of multiple simulation parameters to one identification parameter (Ch. 34.6)

  • Option: Use as absolute value
  • Option: Use as factor

Lin/Log scaling of identification parameters

Lin/Log scaling of residuals

Multiple optimizations with randomized start values (Ch. 34.7.3)

Combining parameter identification with optimization for best suited  partition coefficients/permeability methods (Ch. 34.7.3)

Available optimization algorithms (Ch. 34.7.2)

  • Levenberg-Marquardt
  • Monte Carlo
  • Nelder-Mead (unconstrained)

 Visual feedback during optimization (Ch. 34.8)

  • Time profile
  • Predicted vs. Observed
  • Error history: Total error vs number of evaluations
  • Total error: current/best value
  • Identification parameters: current/best value
  • Export of parameters history to MS-Excel

 Optimization results can be visualized (Ch. 34.8)

  • Time profile
  • Predicted vs. Observed
  • Residuals vs. Time
  • Histogram of Residuals
  • Total error
  • Number of evaluations
  • Identification parameters: min/max/start/best value
  • Warning if best values are "close to" boundaries

Easy cloning of PI configuration within a project (Ch. 34.9.1)

Replacing simulations in PI configuration without losing the settings

Update simulations with optimized parameter values

Export of PI to Matlab (optimization problem can be run in Matlab using any built-in algorithm) (Ch. 34.9.2)

Adding PI configuration to working Journal

Sensitivity analysis (as output of parameter identification) (Ch. 34.8.3.5 ff.)

  • Covariance matrix of identification parameters
  • Correlation matrix of identification parameters
  • 95%- confidence interval of identification parameters

Observed data import supports LLOQ

 

Figure: Parameter Identification - Map outputs to observed data

 

Figure: Parameter Identification - Define Identification Parameters

 

Figure: Parameter Identification - Visual feedback during optimization

 

Figure: Parameter Identification combined with Calculation Methods Variation - Results

 

Furthermore: Smaller and faster installation routine

 

PK-Sim

New building block templates

New compounds, individuals, formulations and application protocols are delivered with the integrated compound database.

 

Fixed issues and Improvements

PK-Sim

47-7790 Should be able to delete a simulation that cannot be loaded

47-8008 Double click on folder, building block, simulation should extend it instead of opening a new window for new folder, building block, simulation

47-7982 After Multiselect of Comparison Plots no right click to get submenu is possible

47-7836 "Immediately dissolve particles smaller than" does not work as expected

47-7844 Intestinal permeability (transcellular) loses formula after cloning

47-8074 Formulation table cannot be loaded

47-7721 In Chart Editor in Standard View the View with the Options Tab cannot be resized to small height

47-7987 Working Journal Page list invisible when page with many related items selected => no navigation in Journal possible

47-7717 Long compound names can’t be selected while importing data

47-8154 Editing meta data/renaming of Observed Data does not change some hidden name

MoBi

46-7251 "Manage user display units" has no effect on table formulas.

46-7152 Exception when changing value of a parameter and switching to another tab without confirming the change

46-7236 Add molecule meta data for observed data importer

46-7019 Comparison between building blocks used in simulations and original building block does not work for spatial structure and events

46-7211 Vmax for Active Transport not contained in Difference

46-7208 Window for "Resolve Merge Conflict" does not keep manually changed size

 

Known issues

If observed data was saved as template, it is not allowed to reload it in the same project (otherwise the project will become corrupted). This applies for both, PK-Sim and MoBi.

If a simulation created in PK-Sim version before 6.1.1 containing a Hepatic or Biliary Plasma Clearance is cloned, the new simulation results may differ from the original one. This is due to the way in which the specific clearance is calculated from the plasma clearances. Intrinsic clearances are calculated from plasma clearances using the well stirred model. These intrinsic clearances are then transformed to specific clearances, which are the internal metric for clearance in PK-Sim. In PK-Sim 6.1, the method used to transform the intrinsic to specific clearance has been slightly altered when using plasma clearances.

Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.

Sensitivity values might be wrong in case of weights unequal 1.

If NaN values are part of an observed data set, the parameter identification cannot handle this reasonably. NaN values should be manually removed from an observed data set before using it in PI.

Cloning simulations in projects saved with PK-Sim version before 5.4.1 may reset some non-formula parameters to default value (#47-6141).

 

 

 

Release Notes for the Systems Biology Software Suite 6.1

New features

PK-Sim

 

  • Oral absorption model improved

New option “Use as suspension” introduced for Weibull, Lint80, Table and Particles Dissolution formulations.

If this option is selected, in the simulation, the tablet will disintegrate in the stomach and the disintegrated particles will migrate along the gastrointestinal tract compartments. The drug release from the particles will depend on the dissolution process selected (Weibull / Table / Particle Dissolution / …).

If this option is not selected, the tablet will be treated as non-disintegrating tablet with discrete transition in the different gastrointestinal tract compartments.

 

  • New compound templates and example projects

New compounds are delivered with the integrated compound database.

Some example projects showing the qualification of the improved oral absorption model against experimental data using compounds from the integrated compound data base are also included now

(Example projects can be found under C:\ProgramData\BTS Products\PK-Sim\6.1\Examples)

  • Adding transporter/enzyme activity in an already created population

User can add new enzyme/transporter/binding partner directly to the population

MoBi

 

  • Improvement of Update/Commit logic between Simulations and Building blocks

Implementation of the update commit logic in MoBi was changed to be consistent with the implementation already available in PK-Sim

PK-Sim and MoBi

 

  • New entry will be added to the project history for every conversion of a project, a simulation or a building block
  • Negative values check for molecule amounts

The negative values check for molecule amounts was introduced in order to warn the user in case some unphysiological negative values are generated in a simulation  (e.g. as a result of bad model parametrization).

Per default, all molecule amounts are assumed to be nonnegative. This default setting can be overridden in the molecule start values building block in MoBi.

If not allowed negative values are generated in a simulation, a warning is shown to the user:

Fixed issues and Improvements

PK-Sim

 

o    47-7743 Load building block from template: sort by name

o    47-7517 Ensure that specific clearance calculated in Hepatic and Biliary Plasma Clearance processes can be used for specific enzymatic processes

o    47-6664 Selected PK-Parameters should be exportable to the clipboard in order to paste them as a table into a slide

o    47-7518 Name of compound associated with observed data during the import should be visible.

o    47-7442 Exception in reuse of Analysis template

o    47-6398 Wrong weight after creation of animal population using non-standard units

o    47-7440 Simulations use the old building block also after modifying the building block

o    47-7528 Adding and removing selected outputs from population analysis causes null reference exception

o    47-7435 Altered units when export results to Excel

o    47-7434 Concentration in Urine

o    47-7511 pkml export: missing name of RHS formulas

o    47-7509 Aging individual does not really work anymore

o    47-7376 Chart export settings for Population simulations

o    47-7581 Wrong Calculation of VSS/F , Vd/F and Total Plasma CL over F

o    47-7127 Copy of an Image of Boxplot (population analysis) does not allow to resize in target application

o    47-7447 Curve selection - problems with grouping and sorting

o    47-7604 PK parameter calculation for observed data

o    47-7595 Reading in ontogeny tables incl. a 0 value produces strange ontogeny factors in population

o    47-7501 Delete on multiple selection does not work as expected

o    47-7470 Renamed Observed Data are displayed with the old name in the curve editor or in the legend

o    47-6782 Run simulation when editor not visible and the analysis will not be shown when editing

o    47-7400 Adding the same enzyme replaces reference values with default values

o    47-7570 Population parameter is not distributed around the value set but around the default

o    47-7416 Scale of preview of imported data is log, but the selection button below shows linear

o    47-7596 Cannot create a user defined administration protocol with target organ "Liver".

o    47-7415 Multiselect of simulations: left mouse click does not work as expected

o    47-7393 Individual scaling: disabled button

o    47-6922 Error configuring simulation if PK analysis is opened

o    47-7432 Loading simulation with mix single and multiple drugs may results in corrupted plot with default display unit is different than the one used by the user settings

o    47-7548 Biliary Clearance to gall bladder not correct for zonated liver

o    47-7499 Flicker in Ontogeny Graph

o    47-7441 Importing a population simulation using a population from file containing advanced parameters

o    47-7534 Default number of cells for InVitro hepatocytes Assays input should be 1M cells per ml

o    47-6067 Default Number of cells for in vitro hepatocytes - residual fraction

o    47-7448 Chart Export Options are missing in Tabbed View / Two Tabs View in Chart Editor

o    47-7390 Column "Value Description" missing in Simulation Parameters for Biochemical processes and Applications

o    47-7414 Compare simulations: wrong description

o    47-7412 Comparison of application protocol building blocks used in simulations is wrong

o    47-7438 In Journal View there should be a button or context menu entry for adding a Journal page

o    47-7405 Compound "Value Descriptions" should be used as Value Description

o    47-7245 Running a simulation defining certain outputs for the figure, results in more outputs than what the user has defined

o    47-7411 Comparison of building blocks in simulations: simulation name not visible

o    47-7329 Always show the item "Column Chooser" in tables column header context menus, in particular in Favorites table

o    47-7401 If Journal Editor is minimized, it is not shown at double click on Journal Page

MoBi

 

o    46-6276 Update passive transport from building block does not work properly

o    46-6987 Changes in Simulation Settings building block cannot be transferred to simulations

o    46-6655 User settings are lost when new version is installed

o    46-7156 Cancel while creating new event in event group throws an exception

o    46-7123 Cannot add new event to even group

o    46-7124 Cannot rename amount observer

o    46-7054 History information is not adequate when editing an explicit formula

o    46-6854 Error loading a simulation if it is already present.

o    46-7046 Configure ignores chosen building block when updating.

o    46-7073 Updating the molecule start values in a simulation from a template and saving the project, the simulation cannot be loaded again

o    46-7112 Cannot load two simulations in MoBi

o    46-7061 Exception on rollback

o    46-6435 Description of passive or active transport is not displayed

o    46-6430 History entry lacks information on MSV changes

o    46-6438 History information on changes in Spatial Structure does not contain building block name

o    46-7024 Import Simulation Parameters: unit dimension of first order rate constants is not properly recognized

o    46-6998 Compare list should show detailed information about changed local Reaction parameter or Molecule property in Simulation

o    46-5584 History improvement

o    46-6828 Molecular Weights used for Observed Data Import should be visible and editable

o    46-5510 Percentile of a distributed parameter is not always adjusted after unit change

o    46-6994 Compare misses differences

o    46-7115 Error after clicking on the Diagram tab within a spatial structure

o    46-5663 Use of a slash in a simulation name prevents starting the parameter identification

o    46-7162 Exception when trying to change Parameter in Favorites view

o    46-6050 Incorrect notification for formula dimension

o    46-7114 Error message for observer without location

o    46-5261 Source and target selection during creation of a passive transports not complete

o    46-6995 Dimension column should not be editable in Favorites of Simulation

o    46-5971 Application tags are not automatically renamed after renaming an application

o    46-6664 Chart Template renaming incomplete

o    46-7040 Drop out message when try to rename Simulation folder

o    46-7144 Molecule Start Values -> Excel import -> Update of description needed

o    46-7142 Renaming of molecule start values does not work

o    46-7105 Cut or paste parameters does not remove the parameter or add parameter in the 'possible referenced objects' view

o    47-7495 Rename alias in explicit formula editor to existing alias does not show validation error or update name

o    46-7055 Adding a parameter to "Molecule Properties" in a spatial structure should also display the path of the parameter (or at least the container above the "Molecule Properties")

o    46-6670 Exception when importing observed data from an excel-file without entries.

o    46-7153 Changing container criteria of a reaction is not recognized as a change in existing simulations.

o    46-6659 Parameter Start Values are not applied correctly.

o    46-7065 No way to load an application if an equally named is present.

o    46-7030 "System.OutOfMemory” exception when deleting too many parameter start values.

o    46-6827 Sorting favorites by name not possible

o    46-7018 Compare observers: no difference after dimension change

o    46-7101 Calculate scale divisor: OK button is active before calculation is finished

o    46-7034 Error converting MoBi 3.4 projects with GFR

o    46-6463 Tag condition for new Parameters in Molecule building blocks cannot be given in Capital Letters

o    46-6862 Parameter Star Values: Changing path does not get recognized

o    46-6869 Importing parameter start values from Excel: It is possible to import parameters with no name and no path

o    46-6868 Importing parameter start values from excel è items with same path è error

o    46-6879 Importing molecule start values from excel è items with same path è error

o    46-6875 Parameter start values è Change Value è Change Path è still counts as element with changed value

o    46-6876 Molecule start values è Change Value è Change Path è still counts as element with changed value

o    46-6880 Importing molecule start values from Excel: It is possible to import parameters with no name and no path

o    46-6280 Change of default units in already existing simulations

o    46-7025 Changing dimension of observer :Message in history is not formatted as expected

o    46-6085 If I change the display units and click "Update", the Chart in the simulation result window remains on those units that were set prior to the simulation. It needs to be re-simulated to be able to get the new units.

o    46-7013 Creating spatial structure: setting the name is not intuitive and it is possible to create a spatial structure using an existing name

o    46-7088 Deleting curve template from template and savingèthe curves are not deleted

o    46-6397 References to Global Reaction Parameters missing in reference tree for molecule start concentration formula

o    46-5505 Rollback to revision crashes

o    46-6461 Double Rollback produces an error

o    46-6789 MoBi in Read-only mode will not open file from the menu

o    46-7047 Creating Simulation fails when parameter of overridden formula is not present

o    46-6719 Excel Export of compare "Path" column

o    46-6648 Cut&Pasted Parameter from Reaction to Container cannot be referenced by reaction any more

o    46-7102 MoBi forgets some User Settings

o    46-6975 Parameter creation cannot be completed once the "state variable" checkbox has been selected

o    46-6396 Copy/Paste parameter reference in a formula garbles up alias

o    46-6425 Parameter tags are not reported

o    46-7056 Opening a working journal file from the windows file explorer with MoBi throws error

o    46-7023 After deleting reaction: edit attention jumps to next reactions building block tab

o    46-6437 Warning text misleading

o    46-6929 Update from Molecules building block resets/deletes Simulation Settings

o    46-6378 Create PK-Sim Molecule and Load Transport wrongly report broken formula

o    46-5448 Value of a discrete distributed parameter cannot be changed after "Reset to Default"

o    46-6426 History comment is not saved to project

o    46-7067 History list shows filter cells in top row

o    46-6424 History entry created upon tagging /adding / removing a parameter lacks path information

o    46-7043 Import of extra organ into PK-Sim model will place the new container too far

o    46-6404 Simulation tree will not open containers after "search"

o    46-7022 Changing a dimension of a parameter will not update the unit in parameter start values and simulations

o    46-7001 Compare displays values in different units

o    46-5851 Empty Formula when defining an Event Assignment

o    46-6175 Update from building block can only be done for all changes

o    46-7002 After commit, the unit cannot be selected

o    46-6966 Simulation settings do not allow compare and commit

o    46-7038 While adding tags to a container list of used tags is not available

o    46-6771 List of Molecule Names in Reaction building block Insert Molecule Dialog is not ordered by name

o    46-7032 Open the same MoBi file does not result in a warning

o    46-7121 Deleting entries from parameter start values takes very long

o    46-6615 Navigating through the list of reactions does not update the "Properties"-frame.

o    46-6981 Working Journal Editor forgets gridline settings and position

o    46-6444 Default Project Chart Template

o    46-6399 Renaming of spatial structure is not renaming elements in Simulation Settings

 

Known issues

·         If observed data was saved as template, it is not allowed to reload it in the same project (otherwise the project will become corrupted). This applies both for PK-Sim and MoBi.

·         Changes in Hepatic and Biliary Plasma Clearances: If a clone of a previous-version simulation containing a Hepatic or Biliary Plasma Clearance is done, the new simulation results may differ from the original simulation. This is due to the way in which the specific clearance was, and is now, calculated from these plasma clearances. Intrinsic clearances are calculated from plasma clearances using the well stirred model. These intrinsic clearances are then transformed to specific clearances, which is the internal metric for clearance in PK-Sim. The method used to transform the intrinsic to specific clearance has been slightly altered when using plasma clearances.

·         Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.

·         The former Matlab-based population simulation toolbox also supported a parameter sensitivity analysis. This feature was decommissioned. Now, sensitivity analyses have to be performed using R or the Matlab Toolbox. We are happy to help out, if you need support, please contact customer support.

·         Cloning simulations in projects saved with PK-Sim version before 5.4.1 may reset some non-formula parameters to default value (#47-6141).

 

 

 

 

 

Release Notes for the Systems Biology Software Suite 6.0

New features

PK-Sim and MoBi

  • Working Journal (Chapter  37)

The Working Journal allows for easy documentation of your working process with the SB Software Suite. Because building PBPK and PD models is often a complex process, documentation is necessary

·         for the modeler to track and review the model building process

·         for handing over a model to colleagues or customers

·         for authorities who have to evaluate the quality of modelling results and would like to see a “run record”

Although it is principally possible to use any text editor to write documentation, the Working Journal of the SB Software Suite provides several features which give additional benefit:

·         Integrated rich text editor with essential formatting options

·         Easy transfer of SB Software Suite content to the Journal (tables, charts)

·         Storage of simulations or building blocks as attachments to Journal Pages which can later be compared to other simulations or even reloaded

·         Fast full text search in the complete Journal

·         Journal Diagram as graphical overview of the model building process

A Working Journal can be shared among several PK-Sim and MoBi project files, so one unique journal can be used within your project even if you use different project files. This makes the Working Journal the ideal tool to connect your thoughts and ideas with your model. Even different users can access the same Working Journal at the same time - but only one user can edit a Journal Page at a time.

After each important work step, intermediate results or decision points can and should be added in a Journal Page to the Journal. This should include the result, the input values, and description of decisions.

For instance, the values of the favorite parameters and result charts can be copied into the Working Journal by copy & paste and corresponding simulations and building blocks can be attached to the Journal Page directly from the context menu.

 

Ribbon “Working Journal” and View “Journal” with list of Journal Pages

Copy & paste of Favorites table into Journal Editor

 Journal Diagram as graphical overview of the model building process

o    Comparison of Building Blocks and Simulations (Chapter  33)

The comparison of building blocks and simulations can help to compare different versions of a model for e.g. reporting purposes. Alterations of individual building blocks can be seen at a glance. Converting models can also lead to alterations in building blocks. This can be the case, if one version of a model uses a functionality of PK-Sim that was not available in the older version. A further, rather special case is a listing of extended start values upon comparison. If parameter or molecule start values are incomplete in MoBi, they are extended during the Create Simulation process. These amended start values will be listed if the respective building blocks before and after creation of a simulation are compared.

 

Comparison of building blocks can also be done within a simulation when a building has been altered and the differences to the original version need to be known.

 

Comparison of building blocks can also be done between two simulations on the same kind of building block

 

 

o    Major enhancements of charts handling  (Chapter  32)

General enhancements

·         Coloring curves with the same color is now easy by drag and drop of colors in the curves table and a new color editor

·         Organizing legends becomes easier by reordering legend entries for curves by drag and drop and hiding dispensable legend entries

·         Default line styles for axes distinguish curves for different y-axes

·         Layout of Chart Editor with selection and width of different columns can be saved to user settings

·         Axis and Curve properties can be accessed by context menus directly in the chart

 

Standard Chart and Font sizes can be defined for export of charts.

After definition of Chart Export Options, charts are always exported in the same size to e.g. Working Journal or slides, independent of the current chart size and of whether preview was selected in the application.


 

User defined templates can be stored for reuse in other simulations.

Chart templates (consisting of axes and curve settings, chart and export options)
can be created from or applied to the current chart.

 

 o    Usability enhancements (multi select, copy/paste of tables)

o    Parameter value description

 

PK-Sim

o    Management of chart templates (Chapter  32)

Chart settings (Chart Options and Chart Export Options, Curve and Axes Options) can be saved in different Chart Templates and reused in a simulation.

o    Management of units (Chapter  35)

Display units can be chosen for a dimension in a project and for a user. In addition, a default display unit for each dimension can be defined.

o    Save/Load of Population simulation analyses

The set of analyses in a population simulation can be saved as template and applied to another population simulation.

o    Clone of analysis (result plots)

MoBi

o    Import of SBML models

SBML models starting from Level 2 Version 1 can be imported as building blocks from which a MoBi model can be created.

o    Favorites

o   Folder structure for Observed data and Simulations

o    Editing of Observed data

o   Better path representation

o   Reaction localization conditions

Reaction creation in the simulations can be controlled via container descriptor conditions

o    Save/Load of observed data in  .PKML format

o    “Plot Parameter” flag can be set in the simulation

o    Save/Load building blocks from templates

 

 

Fixed issues

PK-Sim

o    47-7186 Wrong calculation of enzyme ontogenies for growing individuals

o    47-7169 Wrong Standard deviation value for the Reference concentration of some enzymes

o    47-6947 Wrong calculation of Weibull dissolution with Lag time >0

o    47-6917 Hidden molecular weights for Observed Data

o    47-6639 Keep Expression database paths

o    47-6657 Explanation on empty Scaling Configuration tab

o    47-6656 Hint, if Expression database is not available

o    47-6643 Import of Observed Data: make "Naming pattern" approach more usable

o    47-6946 Chart title is not updated after rename

o    47-7029 Export to clipboard of PK-Analysis with NaN-values crashes the application

o    47-7282 Display of user defined variability is wrong with multiple compounds

o    47-6945 Better Browse for folder dialog

o    47-6223 Export of PK-Analysis should use default settings for units when available

o    47-7249 Ontogeny factor plots: additional explanation of what the variability consists of should be shown.

o    47-7369 Observed data: geometric standard deviation is not correctly shown in Population simulation charts

o    47-7346 Deselected favorites are not updated in the tree for biochemical processes

o    47-7372 Ticks for logarithmic plots in population simulation charts are wrong.

o    47-7324 Population simulation of concentration based MoBi-Import throws an error when doing PK-Analysis

o    47-7351 Project conversion: reconfiguring relative expressions added from Expression database

 

MoBi

o    46-6472 Avoid collapsing and scrolling to the top of the trees and lists after editing values in Molecule Start Values and Parameter Start Values

o    46-5582 Rollback after deleting a neighbour in Spatial Structures causes an error

o    46-6759 Add a Reset button to "Calculate Scale Divisor" dialog

o    46-6776 Molecules building block: display corresponding property page for the selected molecule

o    46-6690 “Create Simulation Settings” button missing in ribbon

o    46-6939 Import from PKML: identical formulas are not recognized

o    46-6369 Negative simulation time can be entered in the settings of a simulation, but throws error upon simulation

o    46-5539 Formula for Application Molecule Builder cannot be selected

o    46-6603 Event|Application cannot be renamed

o    46-6614 "Create process rate parameter" option cannot be deselected

o    46-6098 Chart axis does not show low values

o    46-6780 Changing the dimension of an observer and editing its formula afterwards will destroy the observer

o    46-6793 Error when editing Spatial Structure and clicking zoom icons in tree view

o    46-6733 Metabolites: Urine|Fraction Excreted > 1

o    46-6736 y-Axis assignment of observed data is lost after simulation.

o    46-6782 Dimension of Molecule start amount of a PK-Sim export is lost

o    46-6778 Add PK-Sim Molecule does not create a history entry

o    46-6777 Application of chart template does not work correctly

o    46-6203 Add an option to delete all simulation results

o    46-6787 Diagram for simulations imported from PK-Sim is not shown correctly

o    46-6531 Formula-defined parameter is not copied properly across building blocks

o    46-6808 Setting axis limits does not work well when having two y axis

o    46-6214 Load Reaction mixes concentration and amount based types

o    46-6048 Range warning in “Output Intervals” wrong, when different units are selected

o    46-6680 All curves have the same color in the chart

o    46-6978 Parameter lists with one parameter do not show the property page  for editing the parameter

o    46-6985 Certain concentration curves cannot be displayed in chart

o    46-6923 "Number of recently open projects" can be set to negative number and produces an error

o    46-6499 Bad paths are created in Molecule Start Values and Parameter Start Values after container has been saved

o    46-6912 Update problem after undo delete in Molecule Start Values and Parameter Start Values

o    46-6748 Simulation Settings cannot be committed from simulation to building block after Output Interval or Solver Settings were changed

o    46-5589 Merge cannot load processes with the same name

MoBi Toolbox for Matlab

o    26-5491 NLME crashes if no parameter is limited

o    26-5488 Japanese population not available in the parameter identification toolbox

 Known issues

·         Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.

·         The former Matlab-based population simulation toolbox also supported a parameter sensitivity analysis. This feature was decommissioned. Now, sensitivity analyses have to be performed using R or Matlab Toolbox. We are happy to help out, if you need support, please contact customer support.

·         Cloning simulations in projects saved with PK-Sim version before 5.4.1 may reset some non-formula parameters to default value (#47-6141).

 

 

 

Release Notes for the Systems Biology Software Suite 5.6.3

New features

PK-Sim

o    Drug-drug-interaction:  inhibition of a metabolizing enzyme or transporter by a drug can be defined directly in PK-Sim in a simple and user-friendly manner (an exemplary workflow can be found in the downloadable version of the release notes here:

http://www.systems-biology.com/uc/download.html
(More detailed information in Chapter 16 of the new version’s manual)

 

o    Parent-metabolite simulations: from now on, PK-Sim® offers two alternatives to define drug metabolites. First, metabolites can be a "sink" which means that they are not actively or passively transported. These do not possess editable physico-chemical or ADME properties and cannot be used as compounds in a simulation. Second, compounds in a simulation can be assigned to be a metabolites or other compounds. These metabolites possess physico-chemical and ADME properties and can be transported. In addition, these metabolites can be used in further metabolization reactions and thus metabolic networks can be built. (Chapter 20.2)

 

o    Improved liver structure (“Liver zonation”)

-    Metabolic pathways in the liver are spatially separated along the liver sinusoids. Splitting the liver into more than one zone improves simulation accuracy. (Chapter 12.1.2)

 

o    Improvement of PK-Analysis

- PK-Analysis and simulation chart in the same windows

- PK-Analysis view reorganized

 

o    New Japanese population (data for the age range [0..30] years included)

 

o    Predefined reference concentrations and half-lives for some common enzymes

 

o    Redesign of compound window (Chapter 15)

 

Fixed issues

·        47-6596 Support other delimiters that ";" when reading csv files.

·         47-6727 Plot / Analysis are disappearing under some unknown circumstances

·         26-5476 Crash of simulated annealing

·         47-6604 AUC values in Box Whisker Plot not matching

·         47-6496 Box-plot incomplete Y-axis label and too much numbering

·         47-6495 Rangeplots: do not show the whole range

·         47-6474 Tooltip for format of Ontogeny import missing

·         47-6786 Displayed Concentrion in Lumen-Caecum, etc Colon Ascendenc. etc to high

·         47-6258 Units in solubility Graph cause weired decimal places

·         47-6540 Binning of Range-plots before plotting

·         46-6592 Reactions "Grid" will not disappear once being selected

·         47-2434 Formulation type in the legend of Administration protocol building block

·         46-6468 When selecting a Molecular Parameter, Molecule is not selected

·         47-6468 Fat bars in Population Distribution Tab

·         47-6559 RHS Parameters are not serialized properly when the same formula is used in different parameter using dynamic keywords

·         47-6579 Exported Pivot Table in Ranges values does work properly

·         47-6554 User Defined Variability parameters in simulations are removed when cloning or configuring a simulation and switching the population simulation

·         47-6226 Report uses Lin scale for a plot defined with log scale

·         47-6352 Update from BuildingBlock, removes simulation from "Folder"

·         47-6651 Parameter build mode for molecule transport parameter

·         47-6768 Imported PK-Analyses values are not automatically shown in Analysis window

·         47-6743 No standard deviation for PK parameters in simulation results?

·         47-6807 PK-sim 5.6.1 Build 6128: Revert name composition in PK-analysis - put distinctive feature name first

·         47-6626 PKParameters that are not calculated are shown as not available

·         47-6790 Location of ontogeny factor in the UI

·         47-6605 Error while changing the population

·         47-6812 Curve caption change does not update PK-Analysis header

·         47-6336 PK-Sim (non token Version) opens with token license

·         47-5522 Peripheral venous blood should not be the default for mouse and rat

·         47-6648 Organism Volume Plasma should be visible in PKSim

·         47-6229 Log scale not used in reports for scatter plots X axis

·         46-6639 Unloading DCIMatlabR2013b5_0.dll does not clear memory

·         46-6641 Memory leak in DCIMatlabR2013b5_0.dll

·         47-6780 It is possible to create simulations and save project while in "Read-Only" mode.

·         47-6777 Input fields are not disabled in Read-Only mode.

·         47-6058 Organism|Volume (plasma) != sum of all volumes from plasma-compartments

·         47-6874 Update/Commit to building block does not work after calculating bioavailability

·         46-6665 Error while navigating to parameter from the search

·         46-6667 Exception when importing observed data from an excel-file without entries.

·         47-6673 Error delete age

·         47-6923 Dose Normalized PK Analyzes for Population Analyzes time profiles does not make sense and should be removed

·         47-6870 Set relative expression parameter in simulation: some weird issue with refresh of simulation explorer

 

 

Known issues

·         Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.

·         The former Matlab-based population simulation toolbox also supported a parameter sensitivity analysis. This feature was decommissioned. Now, sensitivity analyses have to be performed using R or Matlab Toolbox. We are happy to help out, if you need support, please contact customer support.

·         Installing SB Suite on Windows 2008 Server requires a manual installation of .NET Framework  3.5 SP1 (download from Microsoft:  http://www.microsoft.com/en-us/download/details.aspx?id=25150).

·         Cloning simulations in projects saved with PK-Sim version before 5.4.1 may reset some non-formula parameters to default value (#47-6141)

 

 ·R   Release Notes for the Systems Biology Software Suite 5.5.3

New features

MoBi

o    Concentration-based reaction networks: it is now possible to define reactions either amount- based or concentration-based;  this choice is made when starting a new project (Chapter 24.1, MoBi-Projects)

o    Free choice of default display units: user is now able to define the default display units per project or per user (Chapter 24.2.7, Default, display and base units)

o    Simulation Settings is defined as building block (Chapter 23.7, Simulation Settings)

o    Scale divisors available in UI. Scale divisors are used to improve the numerical stability of calculations (Chapter 24.11, Import Molecule and Parameter Start Values from Excel)

o    "Create from template" Wizard for PK-Sim like Molecules

o    More functions for Parameter and Molecule Start Values to ease handling (Chapter 24.12, Editing of Molecule and Parameter Start Values)

§  Adding/Removing single parameter start value or molecule start value

§  Refresh dimension for all/selected parameter start values from base Spatial Structure\Molecule Building Block

§  Refresh value for all/selected parameter start values or molecule start values from base Spatial Structure\Molecule Building Block

o    Conflict management in merge function; merge logic is specific for each building block (Chapter 25.9.1, Workflow – Merging simulations into a project)

o    Import Start Values from file (Chapter 24.11, Import Molecule and Parameter Start Values from Excel)

o    Export of reactions, molecules and parameters to Excel as list (Chapter 26.2.3 Export Parts of a Simulation Model)

·      

MoBi Toolbox for MATLAB

o    Moved to Matlab2013b (32 bit)

 

Fixed issues

·         Showing observed data with arithmetic standard deviation and concentration value 0 in Log display might freeze the UI (#47-6215)

·         When dragging a molecule concentration into formula, molecule name is replaced by MOLECULE (#46-6049)

·         Error updating MoBi simulation from a building block (#46-5998)

·         Receptor occupancy wrongly calculated (Previously, receptor occupany was calculated as complex/protein, this was corrected to complex/(protein+complex)) (#47-6134)

·         MoBi Toolbox for Matlab could not find PK-Sim installation folder (#26-5472)

·         Zooming in charts with logarithmic axes does not work properly (#47-6203, # 47-6112)

·         Histogram plots for discrete values not optimal (#47-6266)

·         Renaming a formulation used in a simulation corrupts the simulation (#47-6236)

·         Undo of commit command in MoBi does not work in some cases (#46-6334)

·         Time profile analysis: defining age groups does not accept commas (#47-6240)

·         Export to PDF context menu not defined for simulation folder and comparison folder (#47-6230)

·         Crash after implementing an observer with SumFormula (#46-5941)

·         Parameter Identification toolbox writes values back in MoBi (#46-5978)

·         It is not possible to differentiate applications for different drugs in MoBi (#47-6040)

·         Effective surface area of the GI tract segments for the organism “human” is missing predefined variability parameters. This may lead to minor inaccuracies in absorption variability prediction for the corresponding populations. Median values are not affected. (#47-6500)

(Population simulations created with Versions 5.2 and earlier as well as population simulations not involving oral absorption are not affected.)

Known issues

  • Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.
  • The former Matlab-based population simulation toolbox also supported a parameter sensitivity analysis. This feature was decommissioned. Now, sensitivity analyses have to be performed using R or Matlab Toolbox. We are happy to help out, if you need support, please contact customer support.
  • Cloning simulations in projects saved with PK-Sim version before 5.4.1 may reset some non-formula parameters to default value (#47-6141)

Release Notes for the Systems Biology Software Suite 5.4.3

New features

  •         Improvement of population analysis handling

o    It is now possible to add observed data to time profile analysis

- Meta data can be used for splitting of observed data by pane or by color

o    Observed data is shown in simulation report for time profile analysis

o    PK analysis values can be shown for time profile analysis

o    PK analysis values are shown in simulation report for time profile analysis

o    Export of the raw data from the PK analysis for populations enabled

o    Performance of charts improved

o    It is now possible to change/edit existing groupings

o    Time profile analysis:  exporting data to MS-Excel with original and transposed matrix

  •          New unit dimensions introduced in MoBi for cardiovascular modeling

Fixed issues

  •          Export Comparison Chart to pdf fails (#47- 6224)
  •          Exporting individual simulation to CSV might crash if the project was not saved (#47-6185)
  •       The option to calculate bioavailability after simulation might disappear when reopening an old simulation (#47- 6180)
  •          Changing compound in population simulation might crash (#47-6207)
  •          Tooltip information in the simulations explorer is not shown (#47-6198)
  •          Opening old projects in MoBi might crash under some circumstances (#46-5949)
  •          Population simulations: uptodate status of the plots is not shown (#47-6189)
  •          Crash closing PK-Sim after using Gene expression database (#47-6157)
  •       When cloning a population simulation with analysis using bin grouping and changing the used population, the limits of the bin groupings are not updated (#47-6061)
  •          Problem with Log display for population simulation analysis (#47-6160)
  •          Number of decimals can be defined to generate automatic labels when using a User defined (equally populated) number of bins grouping (#47-6147)
  •          Labels in a User defined (equally populated) number of bins grouping are not editable (#47-6173)

Known issues

  •          Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.
  •          The former Matlab-based population simulation toolbox also supported a parameter sensitivity analysis. This feature was decommissioned. Now, sensitivity analyses have to be performed using R or Matlab Toolbox. We are happy to help out, if you need support, please contact customer support.
  •          Cloning simulations in projects saved with PK-Sim version before 5.4.1 may reset some non-formula parameters to default value (#47-6141)
  •          Showing observed data with arithmetic standard deviation and concentration value 0 in Log display might freeze the UI (#47-6215)

 

Release Notes for the Systems Biology Software Suite 5.4.1

New features

  • Major redesign  of observed data handling:
  • Structuring the observed data into folders in the building blocks explorer
  • Extended meta data for import: (File, Study ID, Molecule, Species, Gender, Dosage, Route, Patient ID, Organ, Compartment)
  • Dynamic meta data can be defined further after import
  • Observed data can be edited after import
  • Preview chart of observed data during import
  • Improvement of simulations handling
  • Structuring simulations into folders in the simulation explorer

Fixed issues

  • Cloning simulations may reset some non-formula parameters to default value (#47-6141)
  • Receptor occupancy wrongly calculated (Previously, receptor occupany was calculated as complex/protein, this was corrected to complex/(protein+complex)) (#47-6134)
  • Event parameter cannot be varied as advanced parameter in population simulations (#47-6025)
  • Chart templating does not work when using multiple simulations (#47-6049)

Known issues

  • Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.
  • The former Matlab-based population simulation toolbox also supported a parameter sensitivity analysis. This feature was decommissioned. Now, sensitivity analyses have to be performed using R or Matlab Toolbox. We are happy to help out, if you need support, please contact customer support.
  • Installing SB Suite on Windows 2008 Server requires a manual installation of .NET Framework  3.5 SP1 (download from Microsoft:  http://www.microsoft.com/en-us/download/details.aspx?id=25150).
  • Cloning simulations in projects saved with PK-Sim version before 5.4.1 may reset some non-formula parameters to default value (#47-6141)

 

Release Notes Systems Biology Software Suite 5.3.2

Bug Fix Release

R    The redesigned and extended Import/Export feature was already launched in 5.3.1. It is described in Chapter 20 of the Systems Biology Software Suite manual.  The Import function allows the user to import individual and population simulations that have been modified outside of the PK-Sim environment, for instance in MoBi. As a result, the user will be able to combine models that were enhanced outside of PK-Sim with populations built in PK-Sim. In addition, the user will be able to simulate advanced scenarios, e.g. if a model was enhanced or built in MoBi to simulate a DDI, the user can import such a model into PK-Sim and perform a simulation.

 

·         The function describing the ontogeny for the UGT1A1 enzyme was optimized. This was realized by an improved fitting function of the established data set.

 

·         The Bug Fix Release 5.3.2 of the Systems Biology Software Suite addresses several issues in PK-Sim and MoBi. Internal bug tracking numbers are: 26-5441, 26-5442, 26-5445, 46-5597, 46-5721, 46-5731, 46-5757,    47-6018, 47-6023, 47-6027, 47-6028, 47-6031, 47-6033, 47-6034, 47-6039, 47-6057, 47-5921, 47-5956, 47-5982    

 

Particularly, the following issues were fixed:

26-5441 Parameter identification doesn’t work for coupled simulations

26-5442 Solver parameters cannot be changed in the MoBi Toolbox for Matlab

46-5597 In MoBi, observer of fraction metabolized may be calculated wrong in projects converted from 3.2 to 3.3.

46-5721, 46-5757 In certain situations, MoBi fails on submitting changes in the simulation back to the building blocks

46-5731 Referencing molecule parameters in reactions in MoBi

47-6018 Project conversion. Some parameters are not available for the variation in populations

47-6023 Configure / Create Simulation with multiple Compounds does not work

47-6027 Formulation parameters are hidden in PK-Sim after import of DDI simulations from MoBi

47-6028 PK-Analysis calculation based on simulation imported from MoBi not flexible enough

47-6033 Corrupted project when using favorites in PK-Sim

47-6057 Importing a simulation from MoBi in PK-Sim: parameter cannot be edited when it was based on a previously defined compound parameter

47-5982 Report: SB Suite Software version with which the report created is not available anymore

 

Known issues

·         Results from population simulations performed in PK-Sim version before 5.2.x cannot be reused in the current platform. The simulation can be loaded, but results need to be re-calculated.

·         The former Matlab-based population simulation toolbox also supported a parameter sensitivity analysis. This feature was decommissioned. Now, sensitivity analyses have to be performed using R or Matlab Toolbox. We are happy to help out, if you need support, please contact customer support.

·         Installing SB Suite on Windows 2008 Server requires a manual installation of .NET Framework  3.5 SP1 (download from Microsoft:  http://www.microsoft.com/en-us/download/details.aspx?id=25150).

·         The SB Suite is not supported in Windows XP (and previous), but installation is not prohibited. However, execution will fail (#47-5950).

·         Changes of formulas in building blocks in MoBi may not trigger the status change of the using simulations  (#46-5773)

 

Release Notes Systems Biology Software Suite 5.3.1

New feature – Population simulation integrated into PK-Sim

Using PK-Sim and MoBi for virtual population studies become substantially more easy and intuitive by a complete redesign: Integrated directly into PK-Sim, publication quality graphical analysis, various import and export function, reporting to PDF, and more (see Chapter 19.4 of the manual for a complete overview). A few representative screenshots are shown below:

·         Analysis: Graphical display of parameters and output can be chosen from e.g. time-profile analysis for concentration-time profile, box whisker, scatter and range plots to visualize distribution of values in a population. This is complemented by flexible grouping feature with either default or customized values for binning and labelling. Different populations and corresponding analyses can be transferred into a comparison chart by “Drag and Drop”. Definition of a reference population is useful to compare e.g. variability within subgroups of a population.

·         PK-Sim models can be extended in MoBi (e.g. adding a tumor) and re-imported into PK-Sim for population simulation studies.

·         Results, and user defined analysis plots are reported to pdf documents.

·         Import/export: Populations, simulation results and PK parameters, MoBi models

·         Simulations are performed in parallel on workstations with multiple cores. Import/export capabilities facilitate the use of high performance compute clusters.

All population simulation functionality is moved from the former ‘Pop Toolbox’ into PK-Sim. Thereby, the Matlab based Toolbox is not supported any longer. The Matlab Parameter Identification Toolbox is still available and supported, likewise the MoBi Toolbox for Matlab and the R Toolbox.   

Known issues

·         Import of MoBi models into PK-Sim for population simulation is possible, but not described in the manual (#47-5956)

·        Results from population simulations from PK-Sim version before 5.2.x and earlier cannot be reused in the current platform. The simulation can be loaded, but results needs to be re-calculated

·         In certain situations, MoBi fails on submitting changes in the simulation back to the building blocks (#46-5721).

·         The previous, Matlab based population simulation toolbox supported, in addition, a parameter sensitivity analysis. This feature has been decommissioned. Sensitivity analyses have to be performed now using the R or Matlab Toolbox. If you need support in using this please contact customer support.

·         Installing SB Suite on Windows 2008 Server requires a manual installation of .NET Framework  3.5 SP1 (downloadable from Microsoft:  http://www.microsoft.com/en-us/download/details.aspx?id=25150).

·     

·         The SB Suite is not supported on Windows XP (and previous) versions, but installation is not prohibited. However, execution will fail (#47-5950).

 

 

Release Notes SB Suite 5.2.1


New features

PK‐Sim

  • Preterm Neonates are added as a special population
  • Individuals can grow during simulation. This is particular useful/required for preterm and term neonates
  • Scaling can be used to change the biometrics of an existing individual, i.e. an adult model may be scaled to an infant model while maintaining/scaling all specific modifications
  • A refined protein model, allowing for example the modeling of antibody drug conjugates
  • New kinetics for active transport processes

MoBi

  • Global search function
  • Warnings and error handling completely re‐designed
  • Several usability improvements

MoBi & PK‐Sim

  • Reporting: Automatic reporting of models and simulation results as pdf document
  • Units handling was redesigned
  • Project file size was reduced, performance of calculations improved
  • Support for Windows 8

Known Issues

General (only Windows 8)

  • The following error message may appear during installation under Windows 8: Initiates file downloadimage

In case of occurrence, click OK and the installation will continue without problems.

  • After Installation under Windows 8, the computer needs to be restarted.

PK‐Sim

  • Preterms and neonates of same age may differ in organ size and blood flow constants. This maylead to discontinuities in PK under certain circumstances for joined populations/analyses
  • Male and female gonads in preterms are identical in the models despite known differences and available data

Mobi

  • An event in a simulation may cause a wrong path replacement of the MOLECULE keyword. As a workaround, manually replace the formula with the MOLECULE path by a new formula containing an absolute reference
  • Canceling simulation creation may cause exception messages, mainly these can be ignored and MoBi will work properly

Basis Toolbox

  • There is an existing issue with former and current units. Users that worked with version 3.1 of the toolbox are strongly recommended to remove the user specific unit list. It can usually be found here: C:\Users\<USERNAME>\AppData\Roaming\BTS Products\MoBiToolboxForMatlab\unitList_3.mat
  • The current toolbox is not compatible with old simulation files. Models have to be imported into MoBi and converted to the 3.2 file version prior processing with toolboxes
  • The R Toolbox is only available for R 2.x, 32 bit version. Other versions may be created by customer request
  • Parameter Identification and Population toolbox require ideally 64bit operation systems and minimum of 8GB ram
  • Special characters on Asian systems may lead to incompatibilities with toolboxes on data import. A workaround is described in the manual (Chapter 39.1.3. Data Definition).

Release Notes SB Suite 5.1.5


The Bug Fix Release 5.1.5 of the Systems Biology Software Suite addresses issues related to wrong
calculations of AUCs and t1/2 under certain circumstances. This has been corrected in the underlying
libraries.


Release Notes SB Suite 5.1.4


The Bug Fix Release 5.1.4 of the Systems Biology Software Suite addresses a gastric empting time (GET) bug:

Issue description:
In PK‐Sim 5, the transit through the small intestine has been defined as a colon arrival time (CAT, or orocaecal transit time, OCTT), corresponding to the time after dosing at which 50% of the drug mass has entered the caecum. This colon arrival time, thus, includes the gastric emptying time (GET), defined as the time at which 63% of drug mass has left the stomach. However, for high GET values in combination with low CAT values, the differential equations cannot be solved because then the GET exceeds the CAT.

Solution:
In this release the problem is fixed by separating the CAT and GET, i.e. switching to a small intestinal transit time (SITT), defined as the time span between gastric emptying and colon arrival.

In addition:

  • Error bar display improved
  • List of parameters available for parameter identification extended

 

Release Notes SB Suite 5.1.3


The Bug Fix Release 5.1.3 of the Systems Biology Software Suite has several bugs fixed and a list of small
feature improvements such as allowing to “clone” simulations. The updated manual reflects all changes
of the software.
Some issues remain:
All of SB Suite

  • Improvement: Excel import of observed data can import text files with arbitrary column separators as well.

PK‐Sim

  • Improvement: Simulations can be ‘cloned’
  • If an ontogeny is selected for a protein (i.e. age specific protein quantities (enzymes, transport, binding partner)), the ontogeny can be visualised
  • Large gastric empting time (GET) values cause difficulties in solving differential equations. In PKSim 5.0, the transit through the small intestine has been defined as a colon arrival time (CAT, or oro‐caecal transit time, OCTT), corresponding to the time after dosing at which 50% of the drug mass has entered the caecum. This colon arrival time, thus, includes the gastric emptying time (GET), defined as the time at which 63% of drug mass has left the stomach. However, for high GET values in combination with low CAT values, the differential equationscannot be solved because then the GET exceeds the CAT.

Currently, GET is limited to species specific upper values:

  • Beagle: 120 min
  • Rat: 155 min
  • Dog: 110 min
  • Monkey: 130 min
  • Minipig: 130 min
  • Mouse: 30 min
  • Human: 90 min

MoBi:

  • Working with larger models and going through longer MoBi sessions may result in "Out of memory" errors, depending on the computer configuration. It is always advisable to periodically save backup copies of the current project.
  • Changing minimum values of a uniform distribution may affect the maximum value of the distribution as well (#5131).

Matlab Toolboxes

  • The GUI of the toolboxes may cause problems when window items are clicked before their buildup is completed. Red warning texts describing ongoing computations are displayed to remind the user to be patient. Only continue your work after a window or tab is displayed completely, in particular on slower computers.
  • The path to the Ghostscript tool should be automatically set. If you receive an error message referring to the "PS2PDF" functionality, please check your user settings. If the path to the program "gswin32c.exe" is empty, you need to insert it manually. Typically, it can be found in the Program Files directory, like "C:\Program Files\gs\gs9.00\bin\gswin32c.exe"

  • Basis Toolbox

    • Supports new table parameters.
    • For table parameters the getParameter function has a new option timeProfile to get interpolated values from underlying table.
    • Parameter Toolbox
    • GUI has been improved in stability, user friendliness and optic.
    • For datasets the user can set a LLOQ value which is then shown in the time profile plots.
    • When plotting takes place the figures are not visible anymore and a progress bar informs the user about progress.
    • Bug fixes.

  • Population Toolbox

    • GUI has been improved in user friendliness and optic.
    • When plotting takes place the figures are not visible anymore and a progress bar informs the user about progress.
    • Bug fixes.

  • R Toolbox

    • Supports new table parameters.
    • For table parameters the getParameter function has a new option TimeProfile to get interpolated values from underlying table.

 

 What is new in Version 5.0.2 

  1. The software manual has been revised from draft to final status.
  2. The expression database descriptions have been revised.
  3. Bug Fixes

 What is New in PK-Sim® 5.0.1

  1. Building block concept: „Individual/Population“, „Compound”, “Administration Protocol”, "Formulation", „Event“ set up as separate and re-usable units.
  2. Population module replaced by building block “Population”
  3. Administration protocols customizable in more detail; more flexibility
  4. History and rollback function added
  5. New fully compartmental gastrointestinal model 
  6. Possibility to define “Events” such as meals and discrete gallbladder emptying
  7. Possibility to model continuous and discrete bile flow in rats
  8. Inclusion of gene expression databases
  9. More flexible display of time windows for simulations
  10. Availability of different GUI-Skins matching mood and season

A more detailed description of the newly available features can be found Opens internal link in current windowhere.


What is New in PK-Sim® 4.2.4

  1. Project files have been restructured to decrease size. However, this causes that files generated or saved with PK-Sim 4.2.4 cannot be read by older versions (of course, the new version reads older versions though).
  2. PK-Analysis has been modified

    • VSS, VD, and Plasma CL are now calculated based on peripheral venous blood (previously it was venous blood)
    • MRT and VSS are only calculated for single applications (NaN are produced when executed based on a multiple administration simulation)

What is New in PK-Sim® 4.2.1

  1. PBPK modeling and simulation of macromolecules, such as therapeutic proteins, is now possible due to the newly developed two-pore model
  2. New Species - Beagle dog.
  3. Refinement of model for peripheral sampling

To see a detailed list of all newly available features in PK-Sim® 4.2 just click here

 

What’s New in PK-Sim® 4.1

  1. Additional Model Structure for a Better Description of Special  Molecule Classes
  2. Switch of Species and New Concept “Specific Clearance”
  3. Scaling of Vmax values
  4. New Units for in vitro Data to Determine Enzyme Kinetics
  5. Calculation of Intestinal Permeability from in-vitro Data
  6. Additional Calculation Methods for Plasma/Organ Partition Coefficients

    • Schmitt Model
    • Poulin & Theil Model
    • Berezhkovskiy Model

  7. New Species – Minipig
  8. New Compartment in Human Model - Saliva
  9. New Application Routes

    • Subcutaneous 
    • Dermal

  10. Reorganization of Graphical User Interface
  11. Summary Plots
  12. Project Report
  13. Redesign of Compound Window
  14. Minor Improvements

To see a detailed list of all newly available features in PK-Sim® 4.1 just click here.

 

What’s new in PK-Sim® 4.0.2

  1. CYP2C19, CYP2C9, CYP2C8 and CYP2B6 have been added to the Clearance Scaling Module.
  2. Minor bug fixes.

Download Update [11.5 MB]

 

What’s new in PK-Sim® 4.0.1

  1. Calculation of organ/plasma partitioning coefficients according to the methods of Rodgers and Rowland (Rodgers and Rowland, 2007) or, optionally, according to the PK-Sim® standard method.
  2. New internal model structure allowing the incorporation of custom PBPK models.
  3. Quicker loading and saving of project files.

 

What’s new in PK-Sim® 3.1.2

  1.  Minor bug fixes.

Download Update

 

What’s new in PK-Sim® 3.1.1

  1. Asian Population (Tanaka, 1996) was added to the PK-Sim® population data base.
  2. PK-Sim®  now works with OS set to non-latin typesets (e.g. Japanese).
  3. Export of PK-Sim® simulations to our new modeling and simulation tool for biological systems MoBi®.  

 

What’s new in PK-Sim® 3.0.6

  1. Minor bug fixes.

 

What’s new in PK-Sim® 3.0.5

  1. The new Statistics Tab allows the user to easily generate bias (+ 95% Confidence Intervals) and precision values to quantitatively compare a simulated curve to observed data. A linear regression analysis can also be performed for the simulated vs. observed data.

 

What’s new in PK-Sim® 3.0.4

  1. The monkey is now included as an additional species.
  2. Minor bug fixes.

 

What’s new in PK-Sim® 3.0.2

  1. Global options are now saved per user.
  2. Concentration unit saved for each plot window separately.
  3. Fraction unbound will be updated after loading a compound from the master or project database.
  4. Possible problems while loading projects are fixed.
  5. User defined settings for distribution parameters saved for use in PK-Pop simulations.
  6. Minor bug fixes.

 

What’s new in PK-Sim® 3.0.1

  1. Clearance Scaling in Children: A clearance scaling module that calculates age dependent clearance in children based on the known adult clearance value and the proportions of eliminating mechanisms involved has been implemented as an add on module in PK-Sim®.
  2. pH Dependent Solubility: Solubility vs. pH is now calculated by PK-Sim® based on pKa values of multiple acidic or basic groups. The solubility vs. pH table can further be edited to make use of existing experimental data.
  3. New Dissolution Module: The new dissolution module calculates the dissolution dynamic of a sold particle formulation moving down the GI tract and is dependent on the particle size distribution and pH-dependent solubility. Different options, such as how the precipitated drug material is treated, are available.
  4. Flexible Administration: The compound can be administered by pre-defined uptake functions (zero- and 1st-order) as well as arbitrary source functions in the form of user-defined mass-time tables into any (sub-)compartment of the model. This flexible administration scheme can be used to model dermal, inhalation, parenteral and other types of administration.
  5. Output of Percentage Metabolized: The fraction of the administered dose metabolized is calculated as additional output. This information is available for each specified metabolic process. It is now possible to model metabolite kinetics in a separate PK-Sim® simulation by inputting the time course of metabolite formation within the (sub)-compartment where metabolism occurs.
  6. Re-Organization of the Graphical User Interface (GUI): The GUI has been re-structured in an even more intuitive manner. The simulation parameters are now organized into four categories: Species, Absorption, Distribution, and Metabolism & Excretion. The input forms for active transporters and metabolism are dynamic and offer more flexibility with respect to the number and type of active process.
  7. Read-Only Mode: PK-Sim® V3.0 can be run in a read-only mode when no valid license is present. The read-only mode provides full access to all previously generated PK-Sim® projects and output data, but does not allow for parameter changes or simulations to be run.
  8. PK-Sim® Absorption Package: A new basis package of PK-Sim® has been released. The Absorption package simulates the gastro-intestinal transit and absorption process and serves the needs of scientists involved in biopharmaceutics and formulation development.

 

 

March 28, 2017

Published in npj Systems Biology and Applications: Translational learning from clinical studies predicts drug pharmacokinetics across patient populations

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December 19, 2016

New publications regarding PBPK modeling: Elderly, Isoniazid, DDI and Diabetes. In addition: A white paper regarding good practices in drug discovery and development

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October 18, 2016

Published in CPT Pharmacometrics & Systems Pharmacology: Applied Concepts in PBPK modeling: How to build a PBPK/PD model

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March 17, 2017

PAGE Meeting 2017, June 06-09, Budapest, Hungary

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October 27, 2016

ACoP Meeting 2016, October 23-26, Seattle, WA, USA

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September 24, 2016

ACCP Annual Meeting 2016, September 25-27, Bethesda, MD, USA

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» All Events