Microdialysis to Assess Free Drug Concentration in Brain

William Kielbasa, Robert Stratford Jr.

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Microdialysis, herein referred to as quantitative microdialysis (QMD), is the only technique that enables sampling of brain extracellular fluid (bECF) in conscious animals to determine the absolute unbound bECF drug concentration. This chapter provides a general overview of the QMD technique and its application in advancing central nervous system (CNS) molecules in the context of model-based drug development. Detection of neurotransmitters in the brain of living organisms was one of the first successful research applications of microdialysis. The capability to collect multiple samples from the same animal combined with more powerful bioanalytical approaches also makes it possible to measure biomarker levels and drug concentrations in the same animal. This approach was used to investigate serotonin response and escitalopram concentrations simultaneously in brain microdialysis samples. Notwithstanding this unique capability of microdialysis, the remainder of the chapter emphasizes the QMD-specific application of the technique.

Original languageEnglish (US)
Title of host publicationBlood-Brain Barrier in Drug Discovery
Subtitle of host publicationOptimizing Brain Exposure of CNS Drugs and Minimizing Brain Side Effects for Peripheral Drugs
Publisherwiley
Pages351-364
Number of pages14
ISBN (Electronic)9781118788523
ISBN (Print)9781118788356
DOIs
StatePublished - Jan 2 2015
Externally publishedYes

Keywords

  • BECF drug concentration
  • Brain extracellular fluid (bECF)
  • Brain microdialysis technique
  • Central nervous system (CNS) molecules
  • Quantitative microdialysis (QMD)

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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