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INDI: a computational framework for inferring drug interactions and their associated recommendations

Assaf Gottlieb, Gideon Y Stein, Yoram Oron, Eytan Ruppin, Roded Sharan

Author Affiliations

  1. Assaf Gottlieb*,1,
  2. Gideon Y Stein2,3,
  3. Yoram Oron2,
  4. Eytan Ruppin1,2 and
  5. Roded Sharan*,1
  1. 1 The Blavatnik School of Computer Science, Tel‐Aviv University, Tel‐Aviv, Israel
  2. 2 Department of Physiology & Pharmacology, Sackler School of Medicine, Tel‐Aviv University, Tel‐Aviv, Israel
  3. 3 Department of Internal Medicine ‘B’, Beilinson Hospital, Rabin Medical Center, Petah‐Tikva, Israel
  1. *Corresponding authors. The Blavatnik School of Computer Science, Tel‐Aviv University, Tel‐Aviv, Israel 69978. Tel.: +972 3 6407139; Fax:+ 972 3 6407139; E-mail: assafgot{at}tau.ac.il or E-mail: roded{at}tau.ac.il
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Abstract

Inferring drug–drug interactions (DDIs) is an essential step in drug development and drug administration. Most computational inference methods focus on modeling drug pharmacokinetics, aiming at interactions that result from a common metabolizing enzyme (CYP). Here, we introduce a novel prediction method, INDI (INferring Drug Interactions), allowing the inference of both pharmacokinetic, CYP‐related DDIs (along with their associated CYPs) and pharmacodynamic, non‐CYP associated ones. On cross validation, it obtains high specificity and sensitivity levels (AUC (area under the receiver‐operating characteristic curve)⩾0.93). In application to the FDA adverse event reporting system, 53% of the drug events could potentially be connected to known (41%) or predicted (12%) DDIs. Additionally, INDI predicts the severity level of each DDI upon co‐administration of the involved drugs, suggesting that severe interactions are abundant in the clinical practice. Examining regularly taken medications by hospitalized patients, 18% of the patients receive known or predicted severely interacting drugs and are hospitalized more frequently. Access to INDI and its predictions is provided via a web tool at http://www.cs.tau.ac.il/∼bnet/software/INDI, facilitating the inference and exploration of drug interactions and providing important leads for physicians and pharmaceutical companies alike.

Synopsis

INDI is a similarity‐based drug–drug interaction prediction method that can infer both pharmacokinetic and pharmacodynamic interactions, as well as their severity levels. Both known and predicted drug interactions are found to be prevalent in clinical practice.

Embedded Image

  • INDI is a similarity‐based drug–drug interaction prediction method, capable of handling both pharmacokinetic and pharmacodynamic interactions.

  • INDI predicts the severity of the interaction and the Cytochrome P450 isozyme involved in pharmacokinetic interactions.

  • We show the prevalence of known and predicted drug interactions in drug adverse reports and in chronic medications taken by hospitalized patients.

Mol Syst Biol. 8: 592

  • Received February 15, 2012.
  • Accepted June 4, 2012.
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This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.

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