Whole-Body Physiologically Based Pharmacokinetic Modeling of GalNAc-Conjugated siRNAs.

ABSTRACT: Background/Objectives: N-acetyl-galactosamine small interfering RNAs (GalNAc-siRNA) are an emerging class of drugs due to their durable knockdown of disease-related proteins. Direct conjugation of GalNAc onto the siRNA enables targeted uptake into hepatocytes via GalNAc recognition of the Asialoglycoprotein Receptor (ASGPR). With a transient plasma exposure combined with a prolonged liver half-life, GalNAc-siRNA exhibits distinct disposition characteristics. We aimed to develop a generic GalNAc-siRNAs whole-body physiologically based pharmacokinetic-pharmacodynamic (WB-PBPK-PD) model for describing the pharmacokinetic-pharmacodynamic (PK-PD) relationship and overall tissue distribution in the open-source platform Open Systems Pharmacology Suite. Methods: Model development was

SUBMITTER: Salim EL 

PROVIDER: S-EPMC11769416 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature