Distinct in vivo target occupancy by bivalent- and induced-fit-like binding drugs.

ABSTRACT:

Background and purpose

Optimal drug therapy often requires long-lasting target occupancy While this attribute was usually linked to the drug's pharmacokinetic properties, the dissociation rate is now increasingly recognized to contribute as well. Nearly all the earlier pharmacokinetic-pharmacodynamic (PK-PD) simulations encompassed single-step binding drugs and focused on k_off . However, 'micro'-PK mechanisms and more complex binding mechanisms like bivalent- and induced-fit binding may contribute as well. Corresponding binding models are presently explored.

Experimental approach

We compared the 24 h in vivo occupancy over time profiles of prototype bivalent- and induced-fit-like binding drugs (A and B) after one or repeated daily dosings, both without and with re

SUBMITTER: Vauquelin G 

PROVIDER: S-EPMC5715606 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature