DILIsym development expands the scope of the software (e.g., extension to other DILI mechanisms) and updates the software to include relevant newly published data. The DILI-sim Initiative approves the particular areas of development, ultimately shaping the focus areas where the DILIsym modeling software will be able to most immediately support drug development programs.
Currently, we are working on developing DILIsym v7A which will include many GUI features to help users model their compounds in the software or replicate clinical protocols. Some of these features include:
- a built-in optimization panel that allows users to construct PBPK representations by comparing software predictions for exposure to preclinical or clinical data
- a clinical monitoring tool to allow dynamic dose modification during simulated clinical trials in response to biomarkers
- additional SimPops that incorporate population variability in ALT levels or mitochondrial biogenesis parameters
- the ability to create SimCohorts quickly and easily
- weight-adjusted dosing option
In addition to the above features, DILIsym v7A has 8 newly added compounds. Tolvaptan and its competitor, lixivaptan, have been included as well as 5 macrolide antiobiotics (azithromycin, clarithromycin, erythromycin, telithromycin, and solithromycin). Bristol-Myers-Squibb (BMS) has also donated the model for their compound BMS-932481, developed by both BMS and DSSI in parallel; both representations are included in v7A!