Predicting drug metabolism induction in silico.
The inducibility of drug-metabolizing enzymes and transporters by numerous xenobiotics has become a vital issue to be considered in the drug development process. Activation of so-called orphan nuclear receptors has been identified to result in increased expression of these detoxifying systems and consequently altered drug levels in the human body. In order to anticipate such mechanisms already in early stages of drug design and to avoid dangerous drug-drug interactions, reliable in silico simulation tools are highly desirable. This review aims to give an introduction into induction of drug metabolism and transport and focuses on computer-assisted molecular modeling prediction techniques, on their applicability and limitations, on recent case studies, and on success stories.
Schuster
Daniela
D
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Innrain 52c, University of Innsbruck, and Center for Molecular Biosciences Innsbruck, CMBI, A-6020 Innsbruck, Austria.
Steindl
Theodora M
TM
Langer
Thierry
T
D000818:Animals; D019295:Computational Biology; D006801:Humans; D008658:Inactivation, Metabolic; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000145:classification / Q000378:metabolism
D004364:Pharmaceutical Preparations; D018160:Receptors, Cytoplasmic and Nuclear