ArticleJournal of pharmacokinetics and pharmacodynamics2021
Minimal brain PBPK model to support the preclinical and clinical development of antibody therapeutics for CNS diseases.
Article in Journal of pharmacokinetics and pharmacodynamics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Minimal physiologically-based hybrid model of pharmacokinetics in pregnant women: Application to antenatal corticosteroids.CPT: pharmacometrics & systems pharmacology · 2023Pooled it
- Intranasal drug delivery to the brain for neurodegenerative diseases: Current efforts and challenges in delivery platforms and modeling.Advanced drug delivery reviews · 2026Review
- Peptide-Based Delivery Systems: Selected Insights into Cell-Penetrating Peptides.ACS chemical neuroscience · 2026Review
- Integrating In-vitro Permeability Assays within PBPK Modeling to Predict CNS Distribution of Standard and Engineered Antibodies.The AAPS journal · 2026Article
- Understanding quantitative effects of anti-amyloid therapies on tau biomarkers and functional outcome. Insights from a comprehensive mechanistic quantitative systems pharmacology study.Frontiers in pharmacology · 2026Article
- Mechanistic modeling of amyloid dynamics relating to Alzheimer's disease progression.Frontiers in aging neuroscience · 2026Article
- Review
- Article
- Modernizing Preclinical Drug Development: The Role of New Approach Methodologies.ACS pharmacology & translational science · 2025Review
- PBPK Modeling: Empowering Drug Development and Precision Dosing in China.CPT: pharmacometrics & systems pharmacology · 2025Review
- Bayesian inference informed by parameter subset selection for a minimal PBPK brain model.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2025Article
- Comparing computational times for simulations when using PBPK model template and stand-alone implementations of PBPK models.Frontiers in toxicology · 2025Article
- Modeling biomarker kinetics of Aβ levels in serum following blast.Frontiers in neurology · 2025Article
- Cerebrospinal Fluid Pharmacokinetics of Nicardipine Following Intrathecal Administration in Subarachnoid Hemorrhage Patients.Journal of clinical pharmacology · 2024Article
- Cerebrospinal Fluid Pharmacokinetics of Nicardipine Following Intrathecal Administration in Subarachnoid Hemorrhage Patients.medRxiv : the preprint server for health sciences · 2023Article
- Utility of Minimal Physiologically Based Pharmacokinetic Models for Assessing Fractional Distribution, Oral Absorption, and Series-Compartment Models of Hepatic Clearance.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Analysis of clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration using a quantitative systems pharmacology model.Scientific reports · 2023Article
- A combined physiologically-based pharmacokinetic and quantitative systems pharmacology model for modeling amyloid aggregation in Alzheimer's disease.CPT: pharmacometrics & systems pharmacology · 2023Article
- A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis.Frontiers in pharmacology · 2023Article
- Revisiting Cerebrospinal Fluid Flow Direction and Rate in Physiologically Based Pharmacokinetic Model.Pharmaceutics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There are several antibody therapeutics in preclinical and clinical development, industry-wide, for the treatment of central nervous system (CNS) disorders. Due to the limited permeability of antibodies across brain barriers, the quantitative understanding of antibody exposure in the CNS is important for the design of antibody drug characteristics and determining appropriate dosing regimens. We have developed a minimal physiologically-based pharmacokinetic (mPBPK) model of the brain for antibody therapeutics, which was reduced from an existing multi-species platform brain PBPK model. All non-brain compartments were combined into a single tissue compartment and cerebral spinal fluid (CSF) compartments were combined into a single CSF compartment. The mPBPK model contains 16 differential equations, compared to 100 in the original PBPK model, and improved simulation speed approximately 11-fold. Area under the curve ratios for minimal versus full PBPK models were close to 1 across species for both brain and plasma compartments, which indicates the reduced model simulations are similar to those of the original model. The minimal model retained detailed physiological processes of the brain while not significantly affecting model predictability, which supports the law of parsimony in the context of balancing model complexity with added predictive power. The minimal model has a variety of applications for supporting the preclinical development of antibody therapeutics and can be expanded to include target information for evaluating target engagement to inform clinical dose selection.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.