A computational approach to predict multi-pathway drug-drug interactions: A case study of irinotecan, a colon cancer medication

Abstract

Drug-drug interactions (DDIs) are a potentially distressing corollary of drug interventions, and may result in discomfort, debilitating illness, or even death. Existing research predominantly considers only a single level of interaction; however, serious health complications may result from multi-pathway DDIs, and so new methods are needed to enable predicting and preventing complex DDIs. This article introduces a novel method for the prediction of DDIs at two pharmacological levels (metabolic and transporter interactions) by means of a rule-based model implemented with Semantic Web technologies. The chemotherapy agent irinotecan is used as a case study for demonstrating the validity of this approach. Mechanistic and interaction data were mined from available sources and then used to predict interactors of irinotecan, including potential DDIs mediated by previously unidentified mechanisms. The findings also draw attention to the profound variation between DDI resources, indicating that clinical practice would see significant value from the development of an evidence-based resource to support DDI identification.

Keywords

• Drug-drug interaction
• Multi-pathway
• Colon cancer
• Irinotecan
• Semantic web technologies
• Prediction