Skip to main content
Open Access Publications from the University of California

An examination of protein binding and protein-facilitated uptake relating to in vitro-in vivo extrapolation.

  • Author(s): Bowman, CM
  • Benet, LZ
  • et al.

As explained by the free drug theory, the unbound fraction of drug has long been thought to drive the efficacy of a molecule. Thus, the fraction unbound term, or fu, appears in equations for fundamental pharmacokinetic parameters such as clearance, and is used when attempting in vitro to in vivo extrapolation (IVIVE). In recent years though, it has been noted that IVIVE does not always yield accurate predictions, and that some highly protein bound ligands have more efficient uptake than can be explained by their unbound fractions. This review explores the evolution of fu terms included when implementing IVIVE, the concept of protein-facilitated uptake, and the mechanisms that have been proposed to account for facilitated uptake.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View