Free phenytoin concentration measurement in brain extracellular fluid: a pilot study

Abstract

We investigate 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 to 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%.

Therapeutic Drug Monitoring in Interstitial Fluid: A Feasibility Study Using a Comprehensive Panel of Drugs

“…To our knowledge, our results for the antirejection drugs are novel, as no literature data on animals or humans are yet available to support these observations. On the contrary, a human study reported phenytoin levels in brain ECF, but found no correlation to phenytoin concentrations in blood 40. However, as the study did not specifically report phenytoin concentrations in ISF, it is unclear what fraction of drug found in ECF could be attributed to the interstitium.…”

Prediction of antiepileptic drug efficacy: the use of intracerebral microdialysis to monitor biophase concentrations

“…The steady-state extracellular phenytoin concentrations corresponded closely to the unbound plasma concentrations. Tisdall et al [83] also found a significant correlation between brain microdialysate and free plasma phenytoin concentration in two patients with acute brain injury. In an extensive study Rambeck et al compared brain extracellular fluid, brain tissue, cerebrospinal fluid and plasma concentrations of different AEDs measured intra-operatively in 22 pharmacoresistant epilepsy patients with complex partial seizures or secondary generalized seizures [84].…”

Multimodal brain monitoring following traumatic brain injury: A primer for intensive care practitioners

“…86 CMD could also help understand the role of brain cytokines, identify biomarkers, and help monitor intracerebral medication levels. [87][88][89][90][91] Ultimately, the use of CMD remains largely investigative, however it does provide the potential to understand cerebral metabolism, which confers different neurophysiologic data from the other aforementioned techniques.…”