Assessment of blood-brain barrier penetration: in silico, in vitro and in vivo

Curr Drug Metab. 2002 Dec;3(6):647-57. doi: 10.2174/1389200023337063.


The amount of drug achieved and maintained in the brain after systemic administration is determined by the agent's permeability at blood-brain barrier (BBB), potential involvement of transport systems, and the distribution, metabolism and elimination properties. Passive diffusion permeability may be predicted by an in silico method based on a molecule's structure property. In vitro cell culture is another useful tool for the assessment of passive permeability and BBB transports (e.g. PGP, MRP). In situ or in vivo techniques like carotid artery single injection or perfusion, brain microdialysis, autoradiography, and others are used at various stages of drug discovery and development to estimate CNS penetration and PK/PD correlation. Each technique has its own application with specific advantages and limitations.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiology*
  • Brain / drug effects
  • Brain / metabolism
  • Computer Simulation
  • Humans
  • Models, Biological*
  • Models, Chemical*
  • Permeability / drug effects
  • Pharmaceutical Preparations / blood
  • Pharmaceutical Preparations / metabolism*


  • Pharmaceutical Preparations