Unit

UNIT 7.11 Cytochrome P450 Inhibition Assays Using Traditional and Fluorescent Substrates

  1. Elsa Paradise,
  2. Prasoon Chaturvedi,
  3. Elena Ter-Ovanesyan

Published Online: 1 DEC 2007

DOI: 10.1002/0471141755.ph0711s39

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Paradise, E., Chaturvedi, P. and Ter-Ovanesyan, E. 2007. Cytochrome P450 Inhibition Assays Using Traditional and Fluorescent Substrates. Current Protocols in Pharmacology. 39:7.11:7.11.1–7.11.12.

Author Information

  1. Surface Logix, Inc., Brighton, Massachusetts

Publication History

  1. Published Online: 1 DEC 2007
  2. Published Print: DEC 2007

Abstract

A key liability in transitioning a new chemical entity (NCE) to a development candidate is NCE-related inhibition (or induction) of cytochrome P450 enzymes, a superfamily of heme-containing oxygenases that are the major route of first-pass metabolism for the majority of marketed drugs. The drawback of a drug/NCE that modulates CYP450 enzyme activity occurs when the compound is co-administered with another drug that relies on the same P450 enzyme for its metabolism. This could result in overdose of the second drug in the case of inhibition, or more rapid metabolism of one or both drugs accompanied by loss of efficacy in the case of enzyme induction. Screening for the inhibition of CYP450 enzymes is now routine in the early stages of evaluating NCEs. This unit describes two inhibition assays using traditional and fluorescent substrates. Curr. Protoc. Pharmacol. 39:7.11.1-7.11.12. © 2007 by John Wiley & Sons, Inc.

Keywords:

  • cytochrome P450 (CYP450);
  • substrate;
  • inhibitor;
  • inhibition constant (IC50);
  • HPLC;
  • LC-MS/MS