The ability to deliver drug molecules effectively\nacross the bloodââ?¬â??brain barrier into the brain is\nimportant in the development of central nervous system\n(CNS) therapies. Cerebral microdialysis is the only existing\ntechnique for sampling molecules from the brain extracellular\nfluid (ECF; also termed interstitial fluid), the\ncompartment to which the astrocytes and neurones are\ndirectly exposed. Plasma levels of drugs are often poor\npredictors of CNS activity. While cerebrospinal fluid (CSF)\nlevels of drugs are often used as evidence of delivery of\ndrug to brain, the CSF is a different compartment to the\nECF. The continuous nature of microdialysis sampling of\nthe ECF is ideal for pharmacokinetic (PK) studies, and can\ngive valuable PK information of variations with time in\ndrug concentrations of brain ECF versus plasma. The\nmicrodialysis technique needs careful calibration for relative\nrecovery (extraction efficiency) of the drug if absolute\nquantification is required. Besides the drug, other molecules\ncan be analysed in the microdialysates for information\non downstream targets and/or energy metabolism in\nthe brain. Cerebral microdialysis is an invasive technique,\nso is only useable in patients requiring neurocritical care,\nneurosurgery or brain biopsy. Application of results to \nwider patient populations, and to those with different\npathologies or degrees of pathology, obviously demands\ncaution. Nevertheless, microdialysis data can provide\nvaluable guidelines for designing CNS therapies, and\nplay an important role in small phase II clinical trials. In\nthis review, we focus on the role of cerebral microdialysis\nin recent clinical studies of antimicrobial agents,\ndrugs for tumour therapy, neuroprotective agents and\nanticonvulsants.
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