ArticlePharmaceutical research2006
Pharmacokinetic consequences of active drug efflux at the blood-brain barrier.
Article in Pharmaceutical research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 62 citations in OpenAlex.
- 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
- Peripherally restricted transthyretin-based delivery system for probes and therapeutics avoiding opioid-related side effects.Nature communications · 2022Article
- Drug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems.Pharmaceutics · 2021Review
- Modeling the Effect of Binding Kinetics in Spatial Drug Distribution in the Brain.Computational and mathematical methods in medicine · 2021Article
- A 3D brain unit model to further improve prediction of local drug distribution within the brain.PloS one · 2020Article
- The need for mathematical modelling of spatial drug distribution within the brain.Fluids and barriers of the CNS · 2019Review
- Imaging P-Glycoprotein Function at the Blood-Brain Barrier as a Determinant of the Variability in Response to Central Nervous System Drugs.Clinical pharmacology and therapeutics · 2019Article
- Heterogeneous drug tissue binding in brain regions of rats, Alzheimer's patients and controls: impact on translational drug development.Scientific reports · 2019Article
- Blood-brain and retinal barriers show dissimilar ABC transporter impacts and concealed effect of P-glycoprotein on a novel verapamil influx carrier.British journal of pharmacology · 2016Article
- Effects of hepatic ischemia-reperfusion injury on the P-glycoprotein activity at the liver canalicular membrane and blood-brain barrier determined by in vivo administration of rhodamine 123 in rats.Pharmaceutical research · 2014Article
- Challenges of using in vitro data for modeling P-glycoprotein efflux in the blood-brain barrier.Pharmaceutical research · 2014Review
- The impact of P-gp functionality on non-steady state relationships between CSF and brain extracellular fluid.Journal of pharmacokinetics and pharmacodynamics · 2013Article
- Advances in PET imaging of P-glycoprotein function at the blood-brain barrier.ACS chemical neuroscience · 2013Review
- Synthesis and small-animal positron emission tomography evaluation of [11C]-elacridar as a radiotracer to assess the distribution of P-glycoprotein at the blood-brain barrier.Journal of medicinal chemistry · 2009Article
- P-glycoprotein deficient mouse in situ blood-brain barrier permeability and its prediction using an in combo PAMPA model.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2009Article
- Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET.European journal of clinical pharmacology · 2009Article
- On the rate and extent of drug delivery to the brain.Pharmaceutical research · 2008Review
- Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2008Article
- Peripheral and central H1 histamine receptor occupancy by levocetirizine, a non-sedating antihistamine; a time course study in the guinea pig.British journal of pharmacology · 2007Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe objective of this simulation study was to investigate how the nature, location, and capacity of the efflux processes in relation to the permeability properties influence brain concentrations.
methodsReduced brain concentrations can be due to either influx hindrance, a gatekeeper function in the luminal membrane, which has been suggested for ABCB1 (P-glycoprotein), or efflux enhancement by transporters that pick up molecules on one side of the luminal or abluminal membrane and release them on the other side. Pharmacokinetic models including passive transport, influx hindrance, and efflux enhancement were built using the computer program MATLAB. The simulations were based on experimentally obtained parameters for morphine, morphine-3-glucuronide, morphine-6-glucuronide, and gabapentin.
resultsThe influx hindrance process is the more effective for keeping brain concentrations low. Efflux enhancement decreases the half-life of the drug in the brain, whereas with influx hindrance the half-life is similar to that seen with passive transport. The relationship between the influx and efflux of the drug across the blood-brain barrier determines the steady-state ratio of brain to plasma concentrations of unbound drug, K(p,uu).
conclusionsBoth poorly and highly permeable drugs can reach the same steady-state ratio, although the time to reach steady state will differ. The volume of distribution of unbound drug in the brain does not influence K(p,uu), but does influence the total brain-to-blood ratio K(p) and the time to reach steady state in the brain.
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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.