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A framework for plasma protein binding: Comparing methods for diverse small molecules and adapting for novel modalities
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DOI:10.1016/j.xphs.2026.104367.png)
Abstract
En 中文
● The study assesses equilibrium dialysis (ED), ultrafiltration (UF), and ultracentrifugation (UC) for plasma protein binding across 26 diverse compounds. It finds strong agreement among these methods, with ED showing high correlation with literature values (R² = 0.97) and both UF and UC (R² = 0.95), indicating their reliability for interchangeable use when acceptance criteria are met. This is confirmed using an additional set of bRo5 or highly bound compounds. ● ED is recommended for its efficiency and lower plasma usage. UF provides an alternative for issues such as plasma stability, whilst UC is recommended for compounds that suffer from non-specific binding (NSB) or failure to diffuse across dialysis membranes. A decision tree aids in selecting methods based on compound characteristics, noting that while ED is most frequently used, UF or UC may be better for certain compounds due to physicochemical properties. ● ED is recommended for its efficiency and lower plasma usage. UF provides an alternative for issues such as plasma stability, whilst UC is recommended for compounds that suffer from non-specific binding (NSB) or failure to diffuse across dialysis membranes. A decision tree aids in selecting methods based on compound characteristics, noting that while ED is most frequently used, UF or UC may be better for certain compounds due to physicochemical properties.
Journal
IF:
3.8
Papers:
1.1W
Citations:
2.6W
Organization
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