Microdialysis for assessing intratumoral drug disposition in brain cancers: a tool for rational drug development.
BACKGROUND
many promising targeted agents and combination therapies are being investigated for brain cancer. However, the results from recent clinical trials have been disappointing. A better understanding of the disposition of drug in the brain early in drug development would facilitate appropriate channeling of new drugs into brain cancer clinical trials.


METHODS
barriers to successful drug activity against brain cancer and issues affecting intratumoral drug concentrations are reviewed. The use of the microdialysis technique for extracellular fluid (ECF) sampling and its application to drug distribution studies in brain are reviewed using published literature from 1995 to the present. The benefits and limitations of microdialysis for performing neuorpharmacokinetic (nPK) and neuropharmacodynamic (nPD) studies are discussed.


RESULTS
the reader will gain an appreciation of the challenges involved in identifying agents likely to have efficacy in brain cancer, an understanding of the general principles of microdialysis, and the power and limitations of using this technique in early drug development for brain cancer therapies.


CONCLUSIONS
a major factor preventing efficacy of anti-brain cancer drugs is limited access to tumor. Intracerebral microdialysis allows sampling of drug in the brain ECF. The resulting nPK/nPD data can aid in the rational selection of drugs for investigation in brain tumor clinical trials.
Johns Hopkins University, Neurosurgery and Oncology, Baltimore, MD 21231, USA. jblakel3@jhmi.edu
Jaishri
J
Blakeley
Jana
J
Portnow
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D017551:Microdialysis / Q000379:methods*; D014018:Tissue Distribution
D000970:Antineoplastic Agents