Considerations in the Use of Cerebrospinal Fluid Pharmacokinetics to Predict Brain Target Concentrations in the Clinical SettingImplications of the Barriers Between Blood and Brain
作者:
Elizabeth C.M. de Lange,
Meindert Danhof,
期刊:
Clinical Pharmacokinetics
(ADIS Available online 2002)
卷期:
Volume 41,
issue 10
页码: 691-703
ISSN:0312-5963
年代: 2002
出版商: ADIS
关键词: Blood brain barrier;Cerebrospinal fluid;Clinical pharmacokinetics
数据来源: ADIS
摘要:
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.
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