期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 41, 期 8, 页码 1797-1820出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X20985946
关键词
Blood-brain barrier; pharmacokinetics; permeability; small molecules; brain vascular volume correction
资金
- National Institutes of Health/National Institute on Drug Abuse [2R01-DA029121, 1R01-DA049737]
- National Institute of Neurological Disorders and Stroke [1 R01NS117906]
This review discusses the significance of the blood-brain barrier in drug delivery and the evolution of different pharmacokinetic techniques in measuring brain uptake and permeability of small molecules. It emphasizes the importance of utilizing the right method to properly assess CNS exposure and acknowledges the progress made while recognizing the need to reduce failures in central nervous system drug development programs.
The brain is the most important organ in our body requiring its unique microenvironment. By the virtue of its function, the blood-brain barrier poses a significant hurdle in drug delivery for the treatment of neurological diseases. There are also different theories regarding how molecules are typically effluxed from the brain. In this review, we comprehensively discuss how the different pharmacokinetic techniques used for measuring brain uptake/permeability of small molecules have evolved with time. We also discuss the advantages and disadvantages associated with these different techniques as well as the importance to utilize the right method to properly assess CNS exposure to drug molecules. Even though very strong advances have been made we still have a long way to go to ensure a reduction in failures in central nervous system drug development programs.
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