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Peer-Reviewed Publication
J Med Chem2025;68(16):16901-16911.August 28, 2025Journal Article

Insights on Volume of Distribution of Acids.

Dennis Smith1, Kevin Beaumont2, Tristan S Maurer3, Li Di4
1Independent, Kent CT14 7AR, U.K.
2AstraZeneca, Cambridge CB2 0AA, U.K.
3Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.
4Recursion Pharmaceuticals, Salt Lake City, Utah 84101, United States.
PubMed DOI

Abstract

Acidic drugs generally have small steady-state volumes of distribution (Vss) around 0.1-0.25 L/kg, due to high binding to serum albumin and low binding to phospholipids in tissues. Acids can reach pharmacological targets in tissues despite small Vss. Enterohepatic recirculation (EHR) of parent drug or reversible acyl glucuronide can increase the Vss of acids. However, rational design to incorporat…

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