Brain microdialysis and applications to drug therapy in severe traumatic brain injury

Pharmacotherapy has a fundamental role in the management of severe traumatic brain injury (TBI). Currently, limited level evidence supports the use of various agents. Overall, the development of drugs for the central nervous system (CNS) has an extremely high failure rate with an estimated 8% of CNS drug candidates becoming clinically available. This is due to the complexity of unique CNS barriers and transport mechanisms that govern (unbound) CNS drug distribution. Improved understanding of CNS drug concentrations, and their relationship to drug response, is needed for more effective and safe drug dosing strategies. Brain microdialysis enables sampling of extracellular (interstitial) brain fluid to obtain unbound drug concentrations at or close to the target site. This information, combined with pharmacokinetic modeling, provides unique opportunities to investigate which drugs are appropriate for CNS treatment to ultimately improve patient-specific drug therapy.