Drug Delivery to the Brain
Physiological Concepts, Methodologies and Approaches
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Elizabeth C.M. de Lange
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Open AccessCNS Viral Infections—What to Consider for Improving Drug Treatment: A Plea for Using Mathematical Modeling Approaches
Neurotropic viruses may cause meningitis, myelitis, encephalitis, or meningoencephalitis. These inflammatory conditions of the central nervous system (CNS) may have serious and devastating consequences if not ...
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Open AccessUsing the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice
The unbound brain extracelullar fluid (brainECF) to plasma steady state partition coefficient, Kp,uu,BBB, values provide steady-state information on the extent of blood-brain barrier (BBB) transport equilibration...
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Professor Margareta Hammarlund-Udenaes - A Humble Scientist Sha** Modern Neuropharmacokinetics
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Open AccessDrug Distribution in Brain and Cerebrospinal Fluids in Relation to IC50 Values in Aging and Alzheimer’s Disease, Using the Physiologically Based LeiCNS-PK3.0 Model
Very little knowledge exists on the impact of Alzheimer’s disease on the CNS target site pharmacokinetics (PK).
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Open AccessThe Extension of the LeiCNS-PK3.0 Model in Combination with the “Handshake” Approach to Understand Brain Tumor Pathophysiology
Micrometastatic brain tumor cells, which cause recurrence of malignant brain tumors, are often protected by the intact blood–brain barrier (BBB). Therefore, it is essential to deliver effective drugs across no...
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Approaches Towards Prediction of CNS PK and PD
It has to be realized that a drug’s pharmacokinetics and pharmacodynamics results from the combination of drug properties and biological system characteristics. This chapter will address the gross anatomy and ...
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Chapter
Disease Influence on BBB Transport in Neurodegeneration
For the pharmacotherapy of neurodegenerative diseases, drugs must pass the blood–brain barrier (BBB). The BBB seems to play an important role in disease initiation and or progression, and many changes in BBB p...
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Book
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Open AccessUnderstanding Drug Delivery to the Brain Using Liposome-Based Strategies: Studies that Provide Mechanistic Insights Are Essential
Brain drug delivery may be restricted by the blood-brain barrier (BBB), and enhancement by liposome-based drug delivery strategies has been investigated. As access to the human brain is limited, many studies h...
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Open AccessLumbar cerebrospinal fluid-to-brain extracellular fluid surrogacy is context-specific: insights from LeiCNS-PK3.0 simulations
Predicting brain pharmacokinetics is critical for central nervous system (CNS) drug development yet difficult due to ethical restrictions of human brain sampling. CNS pharmacokinetic (PK) profiles are often al...
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Open AccessThe 3D Brain Unit Network Model to Study Spatial Brain Drug Exposure under Healthy and Pathological Conditions
We have developed a 3D brain unit network model to understand the spatial-temporal distribution of a drug within the brain under different (normal and disease) conditions. Our main aim is to study the impact o...
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Open AccessEffects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial
Cognitive aging creates major individual and societal burden, motivating search for treatment and preventive care strategies. Behavioural interventions can improve cognitive performance in older age, but effec...
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Mind the Gaps: Ontogeny of Human Brain P-gp and Its Impact on Drug Toxicity
Available data on human brain P-glycoprotein ontogeny during infancy and childhood are limited. This review discusses the current body of data relating to maturation of human brain P-glycoprotein including tra...
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Open AccessThe need for mathematical modelling of spatial drug distribution within the brain
The blood brain barrier (BBB) is the main barrier that separates the blood from the brain. Because of the BBB, the drug concentration-time profile in the brain may be substantially different from that in the b...
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The implications of target saturation for the use of drug–target residence time
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Open AccessCorrection to: Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models
The original version of this article was published open access. Unfortunately, due to a technical issue, the copyright holder name in the online version (HTML and XML) is incorrectly published as “Springer Sci...
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Open AccessModelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models
Drug–target binding kinetics (as determined by association and dissociation rate constants, kon and koff) can be an important determinant of the kinetics of drug action. However, the effect compartment model is u...
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Open AccessTarget and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling
Selectivity is an important attribute of effective and safe drugs, and prediction of in vivo target and tissue selectivity would likely improve drug development success rates. However, a lack of understanding of ...
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Open AccessRevisiting atenolol as a low passive permeability marker
Atenolol, a hydrophilic beta blocker, has been used as a model drug for studying passive permeability of biological membranes such as the blood–brain barrier (BBB) and the intestinal epithelium. However, the e...
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Open AccessFrom receptor binding kinetics to signal transduction; a missing link in predicting in vivo drug-action
An important question in drug discovery is how to overcome the significant challenge of high drug attrition rates due to lack of efficacy and safety. A missing link in the understanding of determinants for dru...
