title: In vivo microdialysis in pharmacological studies of antibacterial agents in the brain.
abstract: Cerebral microdialysis (MD) has proven to be a valuable clinical and research tool in neuroscience. It allows sampling of endogenous and exogenous molecules of interest from the extracellular fluid (ECF) of the brain. MD has also been successfully used to assess drug delivery to the target tissues in pharmacokinetic (PK) studies. There is a concern that due to the blood-brain barrier (BBB), current regimens of commonly used antibiotics might be inadequate. Although PK/pharmacodynamic (PK/PD) studies play an important role in drug evaluation, PK MD studies of antibacterial agents in cerebral tissue are few in number. These studies demonstrate a significant variation in drug penetration in the presence of intracranial pathology. Antibacterial agents from the same chemical group have significantly different PK profiles due to different affinity to the transport proteins of the BBB. Some studies suggest that commonly used antibiotics do not reach a therapeutic concentration range in brain ECF. Studies reviewed in this article are small and performed in different patient populations (brain tumour, head injury, epilepsy) using different methodological approaches to the drug recovery estimation. Nevertheless, they provide interesting and important data on the variability of antibiotic penetration that could be utilized for PK/PD studies and which may have clinical relevance.
authors: University Division of Anaesthesia, Addenbrooke`s Hospital, Hills Road, Cambridge CB2 0QQ, UK. notkinan@doctors.org.uk
authors: N
authors: N
authors: Notkina
authors: C
authors: C
authors: Dahyot-Fizelier
authors: A K
authors: AK
authors: Gupta
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D006801:Humans; D017551:Microdialysis / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents