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

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Abstract

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.

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Acknowledgments

The authors would like to thank Dr. Andy Ayrton for his valuable scientific input during the preparation of this manuscript.

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  1. GlaxoSmithKine R&D, Sir David Jack Research Centre, Ware, SG12 0DP, Hertfordshire, United Kingdom

    Scott G. Summerfield

  2. GlaxoSmithKine R&D China, Zhangjiang Hi-tech Park, Shanghai, 201203, China

    Kelly C. Dong

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  1. Scott G. Summerfield
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  2. Kelly C. Dong
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Correspondence to Scott G. Summerfield.

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Summerfield, S.G., Dong, K.C. In vitro, in vivo and in silico models of drug distribution into the brain. J Pharmacokinet Pharmacodyn 40, 301–314 (2013). https://doi.org/10.1007/s10928-013-9303-7

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  • DOI: https://doi.org/10.1007/s10928-013-9303-7

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