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Drug discovery methods for studying brain drug delivery and distribution
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (PKPD)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (PKPD)
2014 (English)In: Drug delivery to the brain: Physiological concepts, mehtodologies and approaches / [ed] Hammarlund-Udenaes M, de Lange ECM, Thorne R, New York Heidelberg Dordrecht London: Springer , 2014, 271-316 p.Chapter in book (Refereed)
Abstract [en]

Methods used in drug discovery laboratories for assessing the delivery of small molecules to the brain have changed significantly in recent years. There is now more focus on measuring or estimating target unbound-drug concentrations in the brain and evaluating the quantitative aspects of drug transport across the blood-brain barrier (BBB). The techniques for investigation of the rate and extent of BBB transport of new chemical entities (NCEs) are discussed in this chapter. Combinatory methodology for rapid mapping of the extent of brain drug delivery via assessment of the unbound-drug brain partitioning coefficient is presented. The chapter also explains the procedures for approximation of subcellular distribution of NCEs, particularly into the lysosomes. The principles, technical issues, advantages, and potential applications of techniques for evaluation of intra-brain distribution, i.e. equilibrium dialysis-based brain homogenate and brain slice methods, are described. The assessment of extent of BBB transport and intracellular distribution of NCEs, the identification of intra-brain distribution patterns, and their integration with pharmacodynamic measurements are valuable implements for candidate evaluation and selection in drug discovery and development.

Place, publisher, year, edition, pages
New York Heidelberg Dordrecht London: Springer , 2014. 271-316 p.
Series
AAPS advances in the pharmaceutical sciences, ISSN 2210-7371 ; 10
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Science; Pharmacokinetics and Drug Therapy
Identifiers
URN: urn:nbn:se:uu:diva-244791DOI: 10-1007/978-1-4614-9105-7OAI: oai:DiVA.org:uu-244791DiVA: diva2:789855
Available from: 2015-02-20 Created: 2015-02-20 Last updated: 2016-04-29

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Loryan, IrenaHammarlund-Udenaes, Margareta

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