9 Result(s)
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Article
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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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 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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Erratum to: Microdialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations
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Article
Open AccessMicrodialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations
Despite the enormous research efforts that have been put into the development of central nervous system (CNS) drugs, the success rate in this area is still disappointing. To increase the successful rate in the...
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Open AccessEmerging Insights for Translational Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Studies: Towards Prediction of Nose-to-Brain Transport in Humans
To investigate the potential added value of intranasal drug administration, preclinical studies to date have typically used the area under the curve (AUC) in brain tissue or cerebrospinal fluid (CSF) compared ...
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Open AccessDiurnal Variation in P-glycoprotein-Mediated Transport and Cerebrospinal Fluid Turnover in the Brain
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 inve...
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Open AccessPhysiologically Based Pharmacokinetic Modeling to Investigate Regional Brain Distribution Kinetics in Rats
One of the major challenges in the development of central nervous system (CNS)-targeted drugs is predicting CNS exposure in human from preclinical data. In this study, we present a methodology to investigate b...
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Toward the prediction of CNS drug-effect profiles in physiological and pathological conditions using microdialysis and mechanism-based pharmacokinetic-pharmacodynamic modeling
Our ultimate goal is to develop mechanism-based pharmacokinetic (PK)-pharmacodynamic (PD) models to characterize and to predict CNS drug responses in both physiologic and pathologic conditions. To this end, it...
