ArticleFrontiers in physiology2023
A mechanistic pharmacokinetic model for intrathecal administration of antisense oligonucleotides.
Article in Frontiers in physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Safety and toxicity assessment of antisense oligonucleotides in brain-relevant human cellular models.Molecular therapy. Nucleic acids · 2026Review
- Cerebrospinal Fluid Flow Enhancement (CFE) Increases the Spatial Distribution of Methotrexate after Intracerebroventricular Administration in a Sheep Model.Molecular pharmaceutics · 2025Article
- On reduced-order modeling of drug dispersion in the spinal canal.Fluids and barriers of the CNS · 2025Article
- Intrathecal administration of Anti-Nogo-A antibody in macaque monkeys: Pharmacokinetics, tissue penetration and target interaction.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice.Current research in pharmacology and drug discovery · 2025Article
- Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges.Expert opinion on drug discovery · 2025Review
- Article
- Effects of buoyancy on the dispersion of drugs released intrathecally in the spinal canal.Journal of fluid mechanics · 2024Article
- Determination of spinal tracer dispersion after intrathecal injection in a deformable CNS model.Frontiers in physiology · 2023Article
- Nucleic acid-based therapeutics for the treatment of central nervous system disorders.Frontiers in genetics · 2023Review
Corrections and comments
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Authors and funding
5 authors.
Funding
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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 antisense oligonucleotide (ASO) administration in non-human primates. The results are in close agreement with the observed ASO pharmacokinetics in all key compartments of the central nervous system. The model enables determination of optimal injection parameters such as intrathecal infusion volume and duration for maximum ASO delivery to the brain. Our quantitative model-guided analysis is suitable for identifying optimal parameter settings to target specific brain regions with therapeutic drugs such as ASOs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.