Drug Distribution. Part 1. Models to Predict Membrane Partitioning.

ABSTRACT:

Purpose

Tissue partitioning is an important component of drug distribution and half-life. Protein binding and lipid partitioning together determine drug distribution.

Methods

Two structure-based models to predict partitioning into microsomal membranes are presented. An orientation-based model was developed using a membrane template and atom-based relative free energy functions to select drug conformations and orientations for neutral and basic drugs.

Results

The resulting model predicts the correct membrane positions for nine compounds tested, and predicts the membrane partitioning for n = 67 drugs with an average fold-error of 2.4. Next, a more facile descriptor-based model was developed for acids, neutrals and bases. This model considers the partitioning of neutral

SUBMITTER: Nagar S 

PROVIDER: S-EPMC5588161 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature