C-model: A comprehensive enhanced pharmacokinetic/pharmacodynamic simulation environment targeting the complement system

Background and Purpose

Recently, there has been increased research on treatments that modulate the complement system because of its significance in many diseases. However, managing patients with complement-related diseases is challenging owing to the different responses to treatments because of the heterogeneity of the aetiology of the different diseases, which may affect different proteins of the complement activation cascade. This study addresses these challenges using a comprehensive computational model, C-model.

Experimental Approach

C-model is an enhanced pharmacokinetic/pharmacodynamic simulation environment focused on the complement system, which can computationally model the alternative, classical and lectin activation pathways; the terminal/lytic pathway; and their regulation in fluid phase and on erythrocytes and endothelial cells. It incorporates experimental data on patients and simulated drugs.

Key Results

Our study demonstrates that C-model is effective in forecasting complement biomarkers across healthy and diseased states, as well as their reaction to treatments. The simulations from this study are freely available for academic use at https://cmodel.pythonanywhere.com.

Conclusions and Implications

This extensive enhanced pharmacokinetic/pharmacodynamic model supports the development of new therapies and personalised patient management by enabling scenario simulation and adaptation to various complement-related diseases. It advances our understanding of the complement system and its role in disease management.