Evaluation of topiramate neuroprotective effect in severe TBI using microdialysis
| Autor: | Oscar Luis Alves, Aiden J. Doyle, Ross Bullock, Tobias Clausen, Charlotte Gilman |
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| Rok vydání: | 2003 |
| Předmět: |
Topiramate
Microdialysis Time Factors Traumatic brain injury Glutamic Acid Fructose Pharmacology Blood–brain barrier Neuroprotection General Biochemistry Genetics and Molecular Biology History and Philosophy of Science medicine Humans business.industry General Neuroscience Glutamate receptor Human brain medicine.disease Clinical trial medicine.anatomical_structure Neuroprotective Agents Blood-Brain Barrier Brain Injuries business medicine.drug |
| Zdroj: | Annals of the New York Academy of Sciences. 993 |
| ISSN: | 0077-8923 |
| Popis: | Despite recent advances in our understanding of human traumatic brain injury (TBI) pathophysiology, we still need effective neuroprotective agents. The lack of rigorous drug pharmacokinetic studies in the "living" brain is an important cause of neuroprotection trials failure in human TBI research. In the past, several drugs have been labeled as inefficient, and even withdrawn from expensive trials, without knowing their actual penetration in the traumatized human brain. The injured brain is characterized by an increased diffusion distance, due to edema, and reduced blood flow that modulates drug transport across the blood-brain barrier (BBB). In the study reported in this paper, we used cerebral microdialysis to provide a safe and efficient tool for continuous in vivo evaluation of bioavailability and pharmacologic efficacy of topiramate, a glutamate release inhibitor. Topiramate crossed the BBB in neuroprotective concentrations, and showed a lowering effect on glutamate levels, thereby modifying the natural history of glutamate release after TBI. The use of cerebral microdialysis in phase II drug studies will allow the detection of the appropriate therapeutic window and dosage for the neuroprotective agent. This strategy represents a clear improvement compared to traditional clinical trial design, and will reduce the trial costs. |
| Databáze: | OpenAIRE |
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