ArticlePharmaceutical research2023
Physiologically Based Pharmacokinetic Model of Brain Delivery of Plasma Protein Bound Drugs.
Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling of Antidepressants: A Scoping Review of Existing Models, Applications, and Software Tools.Clinical pharmacokinetics · 2026Article
- Assessing the association between multiple indicators of inflammation and sleep disorders in young and middle-aged women: insights from traditional and machine learning approaches.European journal of medical research · 2025Article
- Brain endothelial permeability, transport, and flow assessed over 10 orders of magnitude using the in situ brain perfusion technique.Fluids and barriers of the CNS · 2024Article
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionA physiologically based pharmacokinetic (PBPK) model is developed that focuses on the kinetic parameters of drug association and dissociation with albumin, alpha-1 acid glycoprotein (AGP), and brain tissue proteins, as well as drug permeability at the blood-brain barrier, drug metabolism, and brain blood flow. GOAL: The model evaluates the extent to which plasma protein-mediated uptake (PMU) of drugs by brain influences the concentration of free drug both within the brain capillary compartment in vivo and the brain compartment. The model also studies the effect of drug binding to brain tissue proteins on the concentration of free drug in brain.
methodsThe steady state and non-steady state PBPK models are comprised of 11-12 variables, and 18-23 parameters, respectively. Two model drugs are analyzed: propranolol, which undergoes modest PMU from the AGP-bound pool, and imipramine, which undergoes a high degree of PMU from both the albumin-bound and AGP-bound pools in plasma.
resultsThe free propranolol concentration in brain is under-estimated 2- to fourfold by in vitro measurements of free plasma propranolol, and the free imipramine concentration in brain is under-estimated by 18- to 31-fold by in vitro measurements of free imipramine in plasma. The free drug concentration in brain in vivo is independent of drug binding to brain tissue proteins.
conclusionsIn vitro measurement of free drug concentration in plasma under-estimates the free drug in brain in vivo if PMU in vivo from either the albumin and/or the AGP pools in plasma takes place at the BBB surface.
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