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Assessing and improving the safety of chemicals and the efficacy of drugs depends on an understanding of the biodistribution, clearance, and biological effects of the chemical(s) of interest. A promising methodology for the prediction of these phenomena is physiologically-based pharmacokineticpharmacodynamic (PBPK/PD) modeling, which centers on the prediction of chemical ADME (absorption, distribution, metabolism, and excretion) and the biological effects of the chemical on the organism. A strength of this methodology is that it allows the inclusion and integration of various forms of information across multiple scales of biological organization and facilitates the extrapolation of results across routes of exposure, dosing levels, and species. It is also useful as the foundation for tools to (i) predict biomarker levels given a chemical dose or exposure (forward dosimetry) and (ii) reconstruct a dose given the levels of relevant biomarkers (reverse dosimetry). Despite the importance and promise of PBPK/PD-based approaches to forward and reverse dosimetry, there is currently a lack of user-friendly, freely-available implementations that are accessible and useful to a broad range of users. DoseSim was developed to begin to fill this gap.

The DoseSim framework has built-in functionality for forward dosimetry, forward dosimetry with Monte Carlo (MC), and dose reconstruction simulations using a variety of statistical distributions. It is a user-friendly application with a graphical user interface (GUI) that uses familiar dialogs and widgets for parameter and simulation specification. The GUI also contains flexible methods for specifying the dosing or exposure regimen and the sets of biomarkers for dose reconstruction simulations. Post-processing of results is facilitated through integrated statistical analyses and interactive plotting. Finally, users are allowed to use, modify, and share the code in accordance with the GNU General Public License.

DoseSim provides an extensible framework to conduct a wide variety of dosimetry studies. By incorporating relevant biological, biochemical, physiological, and anatomical data into the underlying model, the tool can provide the user with valuable insights into the ADME and effects of foreign chemicals on human health. We anticipate that chemical-specific application packages utilizing this framework, such as DoseSim:OP for mixtures of organophosphorus insecticides, will provide an important tool to inform studies related to drug disposition and safety and environmental chemical risk.


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DoseSim:OP is currently available for Windows OS (XP, Vista, 7). Versions for other operating systems (Mac OS and Linux) are currently being developed and tested.

A getting started guide is also available.

More information about DoseSim:OP and the underlying PBPK/PD model is available in this paper.

Several example files have been created to help you get started. We are currently expanding this example set and welcome additional examples from our users.

If you are interested in the source code for the project, please contact Brad Reisfeld.