ArticleThe AAPS journal2014
Diurnal variation in P-glycoprotein-mediated transport and cerebrospinal fluid turnover in the brain.
Article in The AAPS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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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.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
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- Circadian Regulation of Neuronal Membrane Capacitance-Mechanisms and Implications for Neural Computation and Behavior.International journal of molecular sciences · 2025Review
- The intersection of circadian rhythms and the blood-brain barrier with drug efficacy and delivery in neurological disorders.Advanced drug delivery reviews · 2025Review
- Circadian influences on central nervous system barriers and the glymphatic system.Frontiers in physiology · 2025Review
- Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery.Circulation research · 2024Review
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- Microfluidic models of the neurovascular unit: a translational view.Fluids and barriers of the CNS · 2023Review
- ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery.Pharmacological reviews · 2023Review
- Acute sleep loss decreases CSF-to-blood clearance of Alzheimer's disease biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Mechanisms behind changes of neurodegeneration biomarkers in plasma induced by sleep deprivation.Brain communications · 2023Article
- Morphine pharmacokinetics and opioid transporter expression at the blood-retina barrier of male and female mice.Frontiers in pharmacology · 2023Article
- Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery.Pharmaceutical research · 2022Review
- Brain Distribution of Drugs: Pharmacokinetic Considerations.Handbook of experimental pharmacology · 2022Article
- Modulation of lymphatic transport in the central nervous system.Theranostics · 2022Review
- Antidepressants and Circadian Rhythm: Exploring Their Bidirectional Interaction for the Treatment of Depression.Pharmaceutics · 2021Review
- First clinical assessment of [Annals of nuclear medicine · 2021Article
- Brain Mechanisms of COVID-19-Sleep Disorders.International journal of molecular sciences · 2021Review
- A circadian clock regulates efflux by the blood-brain barrier in mice and human cells.Nature communications · 2021Article
- Circadian Influences on Chemotherapy Efficacy in a Mouse Model of Brain Metastases of Breast Cancer.Frontiers in oncology · 2021Article
- Timing in drug absorption and disposition: The past, present, and future of chronopharmacokinetics.British journal of pharmacology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nearly all bodily processes exhibit circadian rhythmicity. As a consequence, the pharmacokinetic and pharmacodynamic properties of a drug may also vary with time of day. The objective of this study was to investigate diurnal variation in processes that regulate drug concentrations in the brain, focusing on P-glycoprotein (P-gp). This efflux transporter limits the distribution of many drugs in the brain. To this end, the exposure to the P-gp substrate quinidine was determined in the plasma and brain tissue after intravenous administration in rats at six different time points over the 24-h period. Our results indicate that time of administration significantly affects the exposure to quinidine in the brain. Upon inhibition of P-gp, exposure to quinidine in brain tissue is constant over the 24-h period. To gain more insight into processes regulating brain concentrations, we used intracerebral microdialysis to determine the concentration of quinidine in brain extracellular fluid (ECF) and cerebrospinal fluid (CSF) after intravenous administration at two different time points. The data were analyzed by physiologically based pharmacokinetic modeling using NONMEM. The model shows that the variation is due to higher activity of P-gp-mediated transport from the deep brain compartment to the plasma compartment during the active period. Furthermore, the analysis reveals that CSF flux is higher in the resting period compared to the active period. In conclusion, we show that the exposure to a P-gp substrate in the brain depends on time of administration, thereby providing a new strategy for drug targeting to 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.