Microdialysis in the human brain and its potential role in the development and clinical assessment of drugs.
Neurological injury, as a result of stroke and traumatic brain injury, causes significant morbidity and mortality. Despite the importance of these conditions, the basis of current treatment remains supportive. In recent years, our increasing understanding of the pathophysiological mechanisms of secondary injury, for example excitotoxity, has led to a search for specific agents that can intercept these pathological pathways and act as pharmaceutical neuroprotectants. While successful in the laboratory, these agents have yet to demonstrate efficacy in the clinical arena. The reasons for these failures are varied and incompletely understood, but significant factors include inconclusive pharmacokinetic data, particularly regarding blood brain barrier penetration, and the heterogenous nature of these pathologies in humans. Microdialysis is an established, commercially available, clinical and research tool that is used to sample brain extracellular fluid. It provides the technology to determine the cerebral penetration of drugs and it measures biological markers of brain tissue injury. It can therefore be used to determine the biochemical efficacy of therapeutic manoeuvres. In this review we address the practical application of this technology to the process of drug development.
Helmy
Adel
A
University of Cambridge, Academic Unit of Neurosurgery, Box 167, Level 4, Block A, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
Carpenter
Keri L H
KL
Hutchinson
Peter J
PJ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D002404:Catheterization; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000493:pharmacokinetics
D018377:Neurotransmitter Agents