Role of drug metabolism in drug discovery and development

Med Res Rev. 2001 Sep;21(5):397-411. doi: 10.1002/med.1016.


Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. High metabolic lability usually leads to poor bioavailability and high clearance. Formation of active or toxic metabolites will have an impact on the pharmacological and toxicological outcomes. There is also potential for drug-drug interactions with coadministered drugs due to inhibition and/or induction of drug metabolism pathways. Hence, optimization of the metabolic liability and drug-drug interaction potential of the new chemical entities are some of the most important steps during the drug discovery process. The rate and site(s) of metabolism of new chemical entities by drug metabolizing enzymes are amenable to modulation by appropriate structural changes. Similarly, the potential for drug-drug interactions can also be minimized by appropriate structural modifications to the drug candidate. However, the optimization of the metabolic stability and drug-drug interaction potential during drug discovery stage has been largely by empirical methods and by trial and error. Recently, a lot of effort has been applied to develop predictive methods to aid the optimization process during drug discovery and development. This article reviews the role of drug metabolism in drug discovery and development.

Publication types

  • Review

MeSH terms

  • Animals
  • Biotransformation
  • Cytochrome P-450 Enzyme System / physiology
  • Drug Design*
  • Drug Interactions
  • Enzyme Induction
  • Heme / metabolism
  • Humans
  • Iron / metabolism
  • Pharmaceutical Preparations / metabolism*


  • Pharmaceutical Preparations
  • Heme
  • Cytochrome P-450 Enzyme System
  • Iron