A mechanistic pharmacokinetic model for intrathecal administration of antisense oligonucleotides.

ABSTRACT: Intrathecal administration is an important mode for delivering biological agents targeting central nervous system (CNS) diseases. However, current clinical practices lack a sound theorical basis for a quantitative understanding of the variables and conditions that govern the delivery efficiency and specific tissue targeting especially in the brain. This work presents a distributed mechanistic pharmacokinetic model (DMPK) for predictive analysis of intrathecal drug delivery to CNS. The proposed DMPK model captures the spatiotemporal dispersion of antisense oligonucleotides (ASO) along the neuraxis over clinically relevant time scales of days and weeks as a function of infusion, physiological and molecular properties. We demonstrate its prediction capability using biodistribution data of ant

SUBMITTER: Linninger AA 

PROVIDER: S-EPMC10272745 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature