Precision-cut tissue slices as a tool to predict metabolism of novel drugs

Inge A. M. de Graaf*, Geny M. M. Groothuis, Peter Olinga

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

94 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)879-898
Number of pages20
JournalExpert Opinion on Drug Metabolism & Toxicology
Volume3
Issue number6
DOIs
Publication statusPublished - Dec-2007

Keywords

  • cryopreservation
  • drug induction
  • drug metabolism
  • drug transport
  • precision-cut slices
  • RAT-LIVER SLICES
  • DYNAMIC ORGAN-CULTURE
  • IN-VITRO MODEL
  • RENAL CORTICAL SLICES
  • CYCLOSPORINE-A METABOLISM
  • STELLATE CELL ACTIVATION
  • MULTIWELL PLATE CULTURE
  • HUMAN KIDNEY SLICES
  • LONG-TERM CULTURE
  • LUNG SLICES

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