ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2010
Improved measurement of drug exposure in the brain using drug-specific correction for residual blood.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Utilization of Brain Physiologically Based Pharmacokinetic Modeling in Support of CNS Drug Development: Case Example of Fenebrutinib.The AAPS journal · 2026Article
- Window of opportunity evaluation of blood-brain barrier permeability heterogeneity within and across high-grade glioma patients.Neuro-oncology · 2026Article
- Regional distribution of unbound eletriptan and sumatriptan in the CNS and PNS in rats: implications for a potential central action.The journal of headache and pain · 2024Article
- Active CNS delivery of oxycodone in healthy and endotoxemic pigs.Fluids and barriers of the CNS · 2024Article
- Bystander Effects, Pharmacokinetics, and Linker-Payload Stability of EGFR-Targeting Antibody-Drug Conjugates Losatuxizumab Vedotin and Depatux-M in Glioblastoma Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Analysis of the contributing role of drug transport across biological barriers in the development and treatment of chemotherapy-induced peripheral neuropathy.Fluids and barriers of the CNS · 2024Article
- Pharmacokinetics of 7,8-dihydroxyflavone in neonatal mice with hypoxia-ischemia related brain injury.Frontiers in pharmacology · 2024Article
- Systemic and Brain Pharmacokinetics of Milnacipran in Mice: Comparison of Intraperitoneal and Intravenous Administration.Pharmaceutics · 2023Article
- Active Uptake of Oxycodone at Both the Blood-Cerebrospinal Fluid Barrier and The Blood-Brain Barrier without Sex Differences: A Rat Microdialysis Study.Pharmaceutical research · 2023Article
- Differential Blood-Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro.Pharmaceutics · 2023Article
- Dietary Flavonoids and Adult Neurogenesis: Potential Implications for Brain Aging.Current neuropharmacology · 2023Review
- Unbound Brain-to-Plasma Partition Coefficient, KPharmaceutical research · 2022Article
- Shedding Light on the Blood-Brain Barrier Transport with Two-Photon Microscopy In Vivo.Pharmaceutical research · 2022Article
- Prediction Models for Brain Distribution of Drugs Based on Biomimetic Chromatographic Data.Molecules (Basel, Switzerland) · 2022Article
- Understanding the Blood-Brain Barrier and Beyond: Challenges and Opportunities for Novel CNS Therapeutics.Clinical pharmacology and therapeutics · 2022Review
- Brain Distribution of Drugs: Pharmacokinetic Considerations.Handbook of experimental pharmacology · 2022Article
- Central Nervous System Distribution of an Opioid Agonist Combination with Synergistic Activity.The Journal of pharmacology and experimental therapeutics · 2022Article
- Drug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems.Pharmaceutics · 2021Review
- Understanding the brain uptake and permeability of small molecules through the BBB: A technical overview.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- The Influence of Paracetamol on the Penetration of Sorafenib and Sorafenib N-Oxide Through the Blood-Brain Barrier in Rats.European journal of drug metabolism and pharmacokinetics · 2020Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major challenge associated with the determination of the unbound brain-to-plasma concentration ratio of a drug (K(p,uu,brain)), is the error associated with correction for the drug in various vascular spaces of the brain, i.e., in residual blood. The apparent brain vascular spaces of plasma water (V(water), 10.3 microL/g brain), plasma proteins (V(protein), 7.99 microL/g brain), and the volume of erythrocytes (V(er), 2.13 microL/g brain) were determined and incorporated into a novel, drug-specific correction model that took the drug-unbound fraction in the plasma (f(u,p)) into account. The correction model was successfully applied for the determination of K(p,uu,brain) for indomethacin, loperamide, and moxalactam, which had potential problems associated with correction. The influence on correction of the drug associated with erythrocytes was shown to be minimal. Therefore, it is proposed that correction for residual blood can be performed using an effective plasma space in the brain (V(eff)), which is calculated from the measured f(u,p) of the particular drug as well as from the estimates of V(water) and V(protein), which are provided in this study. Furthermore, the results highlight the value of determining K(p,uu,brain) with statistical precision to enable appropriate interpretation of brain exposure for drugs that appear to be restricted to the brain vascular spaces.
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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.