title: Predicting drug metabolism: experiment and/or computation?
abstract: Drug metabolism can produce metabolites with physicochemical and pharmacological properties that differ substantially from those of the parent drug, and consequently has important implications for both drug safety and efficacy. To reduce the risk of costly clinical-stage attrition due to the metabolic characteristics of drug candidates, there is a need for efficient and reliable ways to predict drug metabolism in vitro, in silico and in vivo. In this Perspective, we provide an overview of the state of the art of experimental and computational approaches for investigating drug metabolism. We highlight the scope and limitations of these methods, and indicate strategies to harvest the synergies that result from combining measurement and prediction of drug metabolism.
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, 8093 Zürich, Switzerland; and the Center for Bioinformatics, University of Hamburg, 20146 Hamburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
authors.affiliation: Global Drug Discovery, Bayer Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Göller
authors.affiliation: Drug Metabolism, Bayer Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Lang
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Jens
authors.initials: J
authors.lastname: Kunze
authors.affiliation: Department of Pharmacy, Lausanne University Hospital, CH-1011 Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Testa
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wilson
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK; and The Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Glen
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods / Q000639:trends*; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods / Q000639:trends*; D005544:Forecasting; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations