Plasma Protein Binding as an Optimizable Parameter for In Vivo Efficacy
Year: 2025
Type: article
Abstract: Plasma protein binding is crucial for understanding pharmacokinetics, pharmacodynamics, and safety. However, it is often not considered to be a primary parameter for optimization in drug design. This study challenges that perspective by revisiting established pharmacokinetic models and analyzing rat pharmacokinetic data of 3357 compounds. Bidirectional strategies for clearance-dependent optimization of plasma protein binding have been elucidated to achieve suitable effective half-lives. The analysis demonstrates that strategically modulating plasma protein binding can enhance drug efficacy and safety, thereby supporting its role as a critical factor in drug design.
Source: Journal of Medicinal Chemistry
Author: Hongtao Zhao
Institution: AstraZeneca (Sweden)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4410820236