Compartmental models for apical efflux by P-glycoprotein--part 1: evaluation of model complexity.

ABSTRACT:

Purpose

With the goal of quantifying P-gp transport kinetics, Part 1 of these manuscripts evaluates different compartmental models and Part 2 applies these models to kinetic data.

Methods

Models were developed to simulate the effect of apical efflux transporters on intracellular concentrations of six drugs. The effect of experimental variability on model predictions was evaluated. Several models were evaluated, and characteristics including membrane configuration, lipid content, and apical surface area (asa) were varied.

Results

Passive permeabilities from MDCK-MDR1 cells in the presence of cyclosporine gave lower model errors than from MDCK control cells. Consistent with the results in Part 2, model configuration had little impact on calculated model errors. The 5-co

SUBMITTER: Nagar S 

PROVIDER: S-EPMC3946900 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature