title: Rebinding: or why drugs may act longer in vivo than expected from their in vitro target residence time.
abstract: BACKGROUND
  It is well established that the in vivo duration of drug action not only depends on macroscopic pharmacokinetic properties like its plasma half-life, but also on the residence time of the drug-target complexes. However, drug 'rebinding' (i.e., the consecutive binding of dissociated drug molecules to the original target and/or targets nearby) can be influential in vivo as well.
  
  
  METHODS
  Information about rebinding is available since the 1980s but it is dispersed in the life sciences literature. This review compiles this information. In this respect, neurochemists and biopohysicians advance the same equations to describe drug rebinding.
  
  
  RESULTS
  The rebinding mechanism is explained according to the prevailing viewpoint in different life science disciplines. There is a general consensus that high target densities, high association rates and local phenomena that hinder the diffusion of free drug molecules away from their target all promote rebinding.
  
  
  CONCLUSIONS
  Simulations presented here for the first time suggest that rebinding may increase the duration and even the constancy of the drug's clinical action. Intact cell radioligand dissociation and related ex vivo experiments offer useful indications about a drug's aptitude to experience target rebinding.
authors: Free University Brussels (VUB), Department of Molecular and Biochemical Pharmacology, Building E.5.10, Pleinlaan 2, B-1050 Brussels, Belgium  +32 2 6291955 ;  +32 2 6291358 ;  gvauquel@vub.ac.be.
authors: Georges
authors: G
authors: Vauquelin