Predicting Drug-Drug Interactions for Premarket Drug Development Process: A Network Based Approach

摘要

pDrug-drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for the safety of the patient but also it is very challenging. In recent years, several drugs have been withdrawn from the market due to interaction related Adverse Events (AEs).pThis study describes a model which can be used to predict novel DDIs based on the similarity of drug interaction candidates to drugs involved in established DDIs which can be used in a large scale to discover novel DDIs. This model is mainly based on the assumption that if drug A and drug B interact to produce a specific biological effect, then drugs similar to drug A (or drug B) are likely to interact with drug B (or drug A) to produce the same effect. We have created a drug network using the 2011 snapshot of a widely used drug safety database which utilizes 352 distinct drugs and contains 3 700 interactions. Then, it was used to develop the proposed model for predicting future DDIs. The target similarities and side effect similarities (P-score) were calculated for all selected pairs of drugs. Then, it was used to develop the proposed model for predicting future DDIs. The proposed model mainly follows two distinct approaches: ‘Which forces the preservation of existing (known) DDIs’ and ‘Without forced to preserve existing DDIs.’ Underneath each of these approaches, three different techniques: target similarity score, side effect similarity (P-score) and resulting score were used to retrieve novel DDIs.pThe proposed model was evaluated using the Drugbank 2014 snapshot as a gold standard for the same set of drugs which produce novel DDIs with an average accuracy of 95% and 92%, average AUC (Area Under the Curve) of 0.9834 and 0.8651 under each of these two approaches respectively.pThe results presented in this study demonstrate the usefulness of the proposed network based drug-drug interaction methodology as a promising approach. The method described in this article is very simple, efficient, and biologically sound.