Considerations in the Use of Cerebrospinal Fluid Pharmacokinetics to Predict Brain Target Concentrations in the Clinical Setting
- 1 January 2002
- journal article
- review article
- Published by Springer Science and Business Media LLC in Clinical Pharmacokinetics
- Vol. 41 (10), 691-703
- https://doi.org/10.2165/00003088-200241100-00001
Abstract
In the clinical setting, drug concentrations in cerebrospinal fluid (CSF) are sometimes used as a surrogate for drug concentrations at the target site within the brain. However, the brain consists of multiple compartments and many factors are involved in the transport of drugs from plasma into the brain and the distribution within the brain. In particular, active transport processes at the level of the blood-brain barrier and blood-CSF barrier, such as those mediated by P-glycoprotein, may lead to complex relationships between concentrations in plasma, ventricular and lumbar CSF, and other brain compartments. Therefore, CSF concentrations may be difficult to interpret and may have limited value. Pharmacokinetic data obtained by intracerebral microdialysis monitoring may be used instead, providing more valuable information. As non-invasive alternative techniques, positron emission tomography or magnetic resonance spectroscopy may be of added value.Keywords
This publication has 119 references indexed in Scilit:
- MR-tomographische Liquorflussmessungen am Spinalkanal mit einem optimierten MRT-Protokoll: Experimentelle und klinische Untersuchungen*RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2001
- Comparison of serum, cerebrospinal fluid and brain extracellular fluid pharmacokinetics of lamotrigineBritish Journal of Pharmacology, 2000
- Ependymal development, proliferation, and functions: A reviewMicroscopy Research and Technique, 1998
- Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A.JCI Insight, 1995
- The ependyma: A protective barrier between brain and cerebrospinal fluidGlia, 1995
- Electroencephalogram Effect Measures and Relationships Between Pharmacokinetics and Pharmacodynamics of Centrally Acting DrugsClinical Pharmacokinetics, 1992
- Recent Advances in Blood-Brain Barrier TransportAnnual Review of Pharmacology and Toxicology, 1988
- A new aspect of the protective functions of the blood-brain barrier: Activities of four drug-metabolizing enzymes in isolated rat brain microvesselsLife Sciences, 1988
- Effects of albumin and .ALPHA.1-acid glycoprotein on the transport of imipramine and desipramine through the blood-brain barrier in rats.CHEMICAL & PHARMACEUTICAL BULLETIN, 1987
- A study of intrathecal, cerebrospinal fluid-to-brain exchangeExperimental Neurology, 1984