Pragmatic approaches to using computational methods to predict xenobiotic metabolism

J Chem Inf Model. 2013 Jun 24;53(6):1282-93. doi: 10.1021/ci400050v. Epub 2013 Jun 11.


In this study the performance of a selection of computational models for the prediction of metabolites and/or sites of metabolism was investigated. These included models incorporated in the MetaPrint2D-React, Meteor, and SMARTCyp software. The algorithms were assessed using two data sets: one a homogeneous data set of 28 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and paracetamol (DS1) and the second a diverse data set of 30 top-selling drugs (DS2). The prediction of metabolites for the diverse data set (DS2) was better than for the more homogeneous DS1 for each model, indicating that some areas of chemical space may be better represented than others in the data used to develop and train the models. The study also identified compounds for which none of the packages could predict metabolites, again indicating areas of chemical space where more information is needed. Pragmatic approaches to using metabolism prediction software have also been proposed based on the results described here. These approaches include using cutoff values instead of restrictive reasoning settings in Meteor to reduce the output with little loss of sensitivity and for directing metabolite prediction by preselection based on likely sites of metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / metabolism
  • Algorithms
  • Analgesics, Non-Narcotic / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Computer Simulation
  • Databases, Pharmaceutical
  • Humans
  • Models, Biological
  • Pharmaceutical Preparations / metabolism*
  • Software


  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Pharmaceutical Preparations
  • Acetaminophen