PHENYTOIN CONCENTRATIONS IN THE HUMAN BRAIN - AN IN-VIVO MICRODIALYSIS STUDY

We report the first human study of phenytoin concentration using in vi vo microdialysis, which permits sampling the extracellular environment of the brain. This technique has been applied to patients undergoing intracranial electrode investigation for intractable epilepsy. By vary ing the rate of perfusion (from 2.5 to 0.25 mu l/min), it is possible to quantify the concentration of drug in the extracellular fluid (ECF) , which reflects the concentration on the outer neuronal cell membrane . Samples were obtained from four catheters in two patients, in whom s erum phenytoin (PHT) concentrations were held constant. Unbound serum concentrations were measured following ultrafiltration at 37 degrees C . In one patient, with left and right hippocampal probes, steady state ECF/unbound serum ratios were 87 and 84% respectively. In the second patient, with hippocampal and frontal probes, ECF/unbound serum ratios were 87 and 85% respectively. Flow rate for 50% maximal recovery aver aged 1.65 mu l/min (1.5-1.7 mu l/min). We found that steady state ECF PHT concentrations corresponded closely to unbound serum concentration s. No differences are observed between different sites within the brai n. Flow rates needed for equilibration of dialysate with the extracell ular space were slower than reported for carbamazepine, but faster tha n those we found for carbamazepine-epoxide and valproate.