Pharmacokinetics and the drug-target residence time concept

Drug Discov Today. 2013 Aug;18(15-16):697-707. doi: 10.1016/j.drudis.2013.02.010. Epub 2013 Mar 14.


The concept of drug-target residence time has been in focus in recent drug discovery literature. However, few studies consider the combined effect of pharmacokinetics (PK) and binding kinetics (BK) on the duration of effect of a drug. Using a simple model that takes both PK and BK into account, we found that prolongation of binding owing to a long drug-target residence time can only occur when the binding dissociation is slower than the PK elimination. Data for several drugs and/or drug candidates in the literature indicate that the opposite is observed, that is, they have a slower elimination compared with dissociation. These observations greatly reduce the usability of drug-target residence times for estimating the duration of effect of a drug in vivo.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Drug Discovery / methods*
  • Drug Discovery / trends
  • Humans
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism*
  • Protein Binding / physiology
  • Proteins / pharmacokinetics


  • Pharmaceutical Preparations
  • Proteins