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Pharmacokinetic concepts in brain drug delivery
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, methodologies and approaches / [ed] Hammarlund-Udenaes M, de Lange ECM, Thorn R, New York Heidelberg Dordrecht London: Springer , 2014, 127-162 p.Chapter in book (Other academic)
Abstract [en]

This chapter presents the pharmacokinetic principles of blood-brain barrier (BBB) transport and the intra-brain distribution of drugs in order to provide a basis for understanding drug delivery to the brain from a clinically relevant perspective. The most important concentrations to measure when determining drug distribution are those of the unbound drug, because it is the unbound drug that causes the pharmacological effect by interacting with the target. Therefore, this chapter also discusses the pharmacokinetic basis, the kind of information provided, and the in vivo relevance of the methods used to obtain reliable, therapeutically useful estimates of brain drug delivery. The main factors governing drug distribution to the brain are the permeability of the BBB to the drug (influx clearance), the extent of nonspecific binding to brain tissue, and the efflux clearance of the drug. The ratio of the influx and efflux clearances provides an estimation of the extent of drug equilibration across the BBB, described by Kp,uu,brain. This parameter is important, as active uptake and/or efflux transporters influence the absolute brain concentrations of unbound drug in relation to those in plasma. The advantage of using Kp,uu,brain during the drug-discovery process lies in its ability to predict the potential success of drugs intended for action within the brain or, conversely, of those with few or no side effects in the brain.

Place, publisher, year, edition, pages
New York Heidelberg Dordrecht London: Springer , 2014. 127-162 p.
, AAPS advances in the pharmaceutical sciences, ISSN 2210-7371 ; 10
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Science
URN: urn:nbn:se:uu:diva-244788DOI: 10.1007/978-1-4614-9105-7ISBN: 978-1-4614-9104-0OAI: oai:DiVA.org:uu-244788DiVA: diva2:789854
Available from: 2015-02-20 Created: 2015-02-20 Last updated: 2015-02-20

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