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Clin Pharmacokinet. 2002;41(10):691-703.

Considerations in the use of cerebrospinal fluid pharmacokinetics to predict brain target concentrations in the clinical setting: implications of the barriers between blood and brain.

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1
Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden, The Netherlands. l.lange@lacdr.leidenuniv.nl

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.

[Indexed for MEDLINE]

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