Physiologically Based Pharmacokinetic Model of Brain Delivery of Plasma Protein Bound Drugs.

ABSTRACT:

Introduction

A physiologically based pharmacokinetic (PBPK) model is developed that focuses on the kinetic parameters of drug association and dissociation with albumin, alpha-1 acid glycoprotein (AGP), and brain tissue proteins, as well as drug permeability at the blood-brain barrier, drug metabolism, and brain blood flow.

Goal

The model evaluates the extent to which plasma protein-mediated uptake (PMU) of drugs by brain influences the concentration of free drug both within the brain capillary compartment in vivo and the brain compartment. The model also studies the effect of drug binding to brain tissue proteins on the concentration of free drug in brain.

Methods

The steady state and non-steady state PBPK models are comprised of 11-12 variables, and 18-23 parameters,

SUBMITTER: Pardridge WM 

PROVIDER: S-EPMC10036418 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature