Computational models for improved estimation of highly plasma-protein-bound compounds

Authors: Ghosh J, Lawless M, Waldman M, Clark RD, Woltosz WS
Conference: ACS
Keywords: bioavailability, computational models, PBPK studies, pharmacokinetic, plasma protein binding
Software: ADMET Predictor®
Division: Simulations Plus

Introduction

Plasma protein binding is an important parameter for characterizing the pharmacokinetics of drug candidates. Binding affinities vary tremendously among compounds, affecting the free fraction in blood, which consequently affects such pharmacokinetic properties as volume of distribution, clearance, bioavailability, and elimination. Only unbound drug can interact with target proteins, so knowing the fraction unbound in plasma (Fup) is especially important for drugs with low Fup and narrow therapeutic index.

248th ACS National Meeting, August 10-14, 2014 San Francisco, CA

By Michael Lawless, Marvin Waldman, Robert D Clark, Walter S Woltosz