Fluorometric screening for metabolism-based drug--drug interactions

J Pharmacol Toxicol Methods. 2000 Jul-Aug;44(1):325-31. doi: 10.1016/s1056-8719(00)00112-x.


Inhibition of cytochromes P-450 (CYP) is a principal mechanism for metabolism-based drug interactions. In vitro methods for quantitatively measuring the extent of CYP inhibition are well-established. Classical methods use drug molecules as substrates and HPLC-based analysis. However, methodologies, which do not require HPLC separations for data acquisition generally offer higher throughputs and lower costs. Multiwell plate-based, direct, fluorometric assays for the activities of the five principal drug-metabolizing enzymes are available and parameters for the use of these substrates to measure CYP inhibition have been established. This methodology is quantitative, rapid, reproducible, and compatible with common high throughput screening instrumentation. This article describes approaches to establishing this methodology in a drug-discovery support program.

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Animals
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors*
  • Drug Interactions*
  • Enzyme Inhibitors / pharmacology*
  • Fluorometry
  • Humans
  • Lansoprazole
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Omeprazole / analogs & derivatives*
  • Omeprazole / pharmacology


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Lansoprazole
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Omeprazole