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Approaches Towards Prediction of CNS PK and PD

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 33))

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Abstract

It has to be realized that a drug’s pharmacokinetics and pharmacodynamics results from the combination of drug properties and biological system characteristics. This chapter will address the gross anatomy and physiology of the central nervous system (CNS) and how physiological processes play a role in CNS drug-target site distribution. This is followed by physiologically based pharmacokinetic (PBPK) model characteristics and the recently developed multi-CNS compartment PBPK models for small molecules and antibodies, with good predictive power for CNS target site distribution in human, as it explicitly distinguishes between drug and systems properties. Understanding the CNS target site concentrations (Stevens et al. 2012) further helps in the development of (PB)PK-pharmacodynamic (PD) models in healthy and disease conditions to further pave the way to predict the right drug at the right location, right time, and right concentration (De Lange 2013a, b).

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Authors and Affiliations

  1. Research Division of Systems Pharmacology and Pharmacy, Leiden University, Leiden, The Netherlands

    Elizabeth C. M. de Lange

  2. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences State University of New York at Buffalo, Buffalo, NY, USA

    Hsueh Yuan Chang & Dhaval Shah

Authors
  1. Elizabeth C. M. de Lange
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  2. Hsueh Yuan Chang
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  3. Dhaval Shah
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Correspondence to Elizabeth C. M. de Lange .

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Editors and Affiliations

  1. Research Division of Systems Pharmacology and Pharmacy, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  2. Department of Pharmacy, Uppsala University, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  3. Biology Discovery, Denali Therapeutics, South San Francisco, CA, USA

    Robert G. Thorne

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Lange, E.C.M.d., Chang, H.Y., Shah, D. (2022). Approaches Towards Prediction of CNS PK and PD. In: de Lange, E.C., Hammarlund-Udenaes, M., Thorne, R.G. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 33. Springer, Cham. https://doi.org/10.1007/978-3-030-88773-5_12

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