title: Free phenytoin concentration measurement in brain extracellular fluid: a pilot study.
abstract: This article investigates the relationship between brain extracellular fluid free phenytoin concentration and plasma free phenytoin concentration in adults with acute brain injury. Daily cerebral microdialysate free phenytoin concentration was measured in eight adults with acute brain injury and compared with simultaneous measurement of plasma free phenytoin concentration. The group data revealed no significant correlation between microdialysate and plasma free phenytoin concentration (r = 0.34, p = 0.41). However, in two patients, with a sufficient number of samples for intra-individual analysis, there was a significant correlation between microdialysate and plasma free phenytoin concentration (r = 0.92, p < 0.001 and r = 0.88, p < 0.01). In vitro microdialysis relative recovery for phenytoin was 2.1%. In the context of acute brain injury, measurement of free plasma phenytoin concentration may not provide an accurate reflection of regional brain extracellular fluid free phenytoin concentration and may have limitations with respect to achieving reproducible brain extracellular fluid free phenytoin concentrations. This has implications for dosing regimens relying on plasma phenytoin levels.
authors.affiliation: Department of Neuroanaesthesia and Neurocritical Care, National Hospital for Neurology and Neurosurgery, London, UK. martin.tisdall@uclh.nhs.uk
authors.forename: M
authors.initials: M
authors.lastname: Tisdall
authors.forename: S
authors.initials: S
authors.lastname: Russo
authors.forename: J
authors.initials: J
authors.lastname: Sen
authors.forename: A
authors.initials: A
authors.lastname: Belli
authors.forename: N
authors.initials: N
authors.lastname: Ratnaraj
authors.forename: P
authors.initials: P
authors.lastname: Patsalos
authors.forename: A
authors.initials: A
authors.lastname: Petzold
authors.forename: N
authors.initials: N
authors.lastname: Kitchen
authors.forename: M
authors.initials: M
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000032:analysis* / Q000097:blood; D001923:Brain Chemistry; D001930:Brain Injuries / Q000150:complications / Q000175:diagnosis; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D045604:Extracellular Fluid / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010672:Phenytoin / Q000032:analysis* / Q000097:blood; D010865:Pilot Projects
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin