White Paper

Pharmacokinetic Strategies In CNS Drug Discovery

nervous system

Our understanding of the design and functioning of the Central Nervous System has dramatically improved over the last two decades. In spite of this, the discovery and clinical development of drugs for many CNS disorders has remained elusive. New drugs targeting important CNS diseases in general have higher failure rates than the other diseases, both preclinically and clinically.

During the preclinical stage, it is relatively more difficult to make findings in CNS disease that can be translated into a successful clinical candidate than in most other areas. The reason for this difficulty is the presence of the blood-brain barrier (BBB), which limits the entry of molecules into the CNS. Commonly used techniques to increase penetration by small molecules, such as enhanced lipophilicity, can dramatically reduce solubility, leading to difficulties in drug delivery. Many classes of large molecules, such as peptides and antibodies, will not readily access the CNS without some form of assisted transport. This is the reason pharmacokinetics of the drug, along with the drug delivery mechanisms, play an important role in determining the success of new CNS drugs.

We shall discuss some successful PK approaches that we have employed in the recent past and may help in CNS targeted drug discovery and development efforts.

 

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