Long-lasting target binding and rebinding as mechanisms to prolong in vivo drug action.

ABSTRACT: An increasing number of examples in the literature suggest that the in vivo duration of drug action not only depends on macroscopic pharmacokinetic properties like plasma half-life and the time needed to equilibrate between the plasma and the effect compartments, but is also influenced by long-lasting target binding and rebinding. The present review combines information from different research areas and simulations to explore the nature of these mechanisms and the conditions in which they are most prevalent. Simulations reveal that these latter phenomena become especially influential when there is no longer sufficient free drug around to maintain high levels of receptor occupancy. There is not always a direct link between slow dissociation and long-lasting in vivo target protection, as the

SUBMITTER: Vauquelin G 

PROVIDER: S-EPMC2990149 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature