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Simultaneous brain (gray matter) and serum specimens from 18 patients treated with oral phenytoin, who underwent cortical resections for intractable seizures, were analyzed by HPLC. The correlation between brain phenytoin concentration and unbound (free) phenytoin (r = 0.98-0.99) was significantly better than the correlation between brain phenytoin and total serum phenytoin (r = 0.90-0.93). Phenytoin concentrations in tissue from epileptic foci were slightly lower than brain phenytoin concentrations in non-epileptic regions in the same patient (means 15.0 vs. 15.5 micrograms/g, P less than 0.05). The results support the value of monitoring unbound phenytoin in clinical situations where phenytoin binding is highly variable.
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