Precision-cut tissue slices as a tool to predict metabolism of novel drugs.
Precision-cut tissue slices have been applied by many researchers because they represent an organ mini-model that closely resembles the organ from which it is prepared, with all cell types present in their original tissue-matrix configuration. Preparation and incubation methods of precision-cut tissue slices from various tissues are discussed and recommendations are given for optimal handling and culturing to retain optimal viability and functional integrity. The potential of precision-cut tissue slices from several organs to predict metabolite profiles and metabolic clearance of novel drugs, the involvement of transporters and the induction and inhibition of drug metabolism is discussed. To allow regular use of tissue slices in drug discovery and development, improvement of cryopreservation methods for precision-cut tissue slices is of great importance. It is concluded that the use of tissue slices in the pharmaceutical industry and in academic research can contribute significantly to obtain relevant information about metabolism and drug-drug interactions in various organs and pharmacokinetics of novel chemical entities in man, and thereby to the development of safe drugs.
Graaf
Inge Am de
IA
University of Groningen, Department of Pharmacokinetics and Drug Delivery, Research Institute for Pharmacy, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. I.A.M.de.Graaf@rug.nl
Groothuis
Geny Mm
GM
Olinga
Peter
P
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008867:Microtomy / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System