In vitro, in vivo and in silico models of drug distribution into the brain

Achieving sufficient brain penetration to elicit efficacy in humans is one of the most challenging tasks for scientists in CNS Drug Discovery. Substantial progress has been made in the past decade in understanding the factors influencing the rate and extent of brain distribution via a variety of in...

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Bibliographic Details
Published in:Journal of pharmacokinetics and pharmacodynamics 2013-06, Vol.40 (3), p.301-314
Main Authors: Summerfield, Scott G., Dong, Kelly C.
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Brain - metabolism
Cell Line
Central Nervous System Agents - blood
Central Nervous System Agents - chemistry
Central Nervous System Agents - pharmacokinetics
Drug Discovery - methods
Humans
Models, Biological
Pharmacology/Toxicology
Pharmacy
Review Paper
Structure-Activity Relationship
Substrate Specificity
Tissue Distribution
Veterinary Medicine/Veterinary Science
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Summary:Achieving sufficient brain penetration to elicit efficacy in humans is one of the most challenging tasks for scientists in CNS Drug Discovery. Substantial progress has been made in the past decade in understanding the factors influencing the rate and extent of brain distribution via a variety of in vivo, in vitro and in silico methodologies, and hence, predict their likelihood of success in man. This purpose of this review is to summarize the current approaches with a special focus on parameters related to free drug concentrations in brain which are the most pharmacologically relevant for the majority of CNS disease targets. Due to the dynamic and complex nature of this targeted organ, it is inevitable that these approaches have not been able to provide a fully comprehensive assessment of brain distribution and are expected to evolve further in the years to come.
ISSN:1567-567X
1573-8744
DOI:10.1007/s10928-013-9303-7