PKPD_Project

To generate the desired .mat files and figures, first run all the MATLAB code files in this order:

1. Levetiracetam_build_model.m
2. LEV_Sens_Analysis.m
3. LEV_GSA.m
4. LEV_PopVar.m
5. LEV_missed_dose.m
6. LEV_missed_dose_consecutive.m

Then run the visualization code to generate the figures and app:

1. Mass_balance_vis.R (Figure 3)
2. Lev_ConcCurve.R (Figure 4)
3. single_dose_repeated_dose.R (Figures 5 and 6)
4. LEV_Sens_Analysis.R (Figure 7)
5. LEV_GSA.R (Figure 8)
6. LEV_PopVar.R (Figures 9-11)
7. LEV_missed_dose_vis.R (Figure 12)
8. missed_dose_pop_histogram.R (Figures 13 and 14)
9. app.R (Shiny App: link access: https://connie-chang-chien.shinyapps.io/PKPD_Project_Levetiracetam/?_ga=2.144305398.210535369.1651115737-794475808.1649938165)

File Descriptions:

Equations and Simulation Code:

• Levetiracetam_eqns.m contains the PK model equations.
• Levetiracetam_sim.m is the function called to run the simulation. This function outputs all of the key metrics (concentrations, effects, AUC, AUEC, Ctrough, and Etrough)

Model building: (all generated .mat files and figures are saved to the build_model_data folder)

• LEV SV2A occupancy seizure protection correlation.xlsx shows the linear correlation between SV2A occupancy and seizure protection extracted from literature. These extracted linear fits are shown in Figure 2 and used to build PD models.
• Levetiracetam_build_model.m builds the model and generates the data for Figures 3-6.
• Mass_balance_vis.R generates Figure 3.
• Lev_ConcCurve.R generates Figure 4.
• Single_dose_repeated_dose.R generates Figures 5 and 6.

Sensitivity Analysis: (all generated .mat files and figures are saved to the sens_analysis_data folder)

• LEV_Sens_Analysis.m runs the local sensitivity analysis and generates the data for Figure 7.
• LEV_Sens_Analysis.R generates Figure 7.
• LEV_GSA.m runs the global sensitivity analysis and generates the data for Figure 8.
• LEV_GSA.R generates Figure 8.

Population Variability: (all generated .mat files and figures are saved to the pop_var_data folder)

• LEV_PopVar.m generates a virtual population and runs the population variability analysis, outputting the data for Figures 9-11.
• LEV_PopVar.R generates Figures 9-11.

Missed Dose Analysis: (all generated .mat files and figures are saved to the missed_dose_data and missed_dose_pop_data folders)

• LEV_missed_dose.m runs the missed dose analysis and generates data for Figures 12-14.
• LEV_missed_dose_vis.R generates Figures 12.
• missed_dose_pop_histogram.R generates Figures 13 and 14.

Shiny app: (all generated .mat files and figures are saved to the data subfolder of the PKPD_Project_Levetiracetam_APP folder)

• Levetiracetam_sim_missed_dose_consecutive.m is the function called to run the missed dose simulation for consecutive missed doses.
• LEV_missed_dose_consecutive.m runs the consecutive missed dose analysis and generates data for the Shiny app (Figure 17).
• app.R generates the Shiny app.