Importance of unbound phenytoin serum levels in head trauma patients.

Total (bound + unbound) and unbound phenytoin serum concentrations were measured in ten male comatose head trauma patients and ten male epileptic patients. Serum biochemistry and complete blood cell counts were normal for both groups, except albumin concentrations were below normal in the head trauma patients for nutritional reasons. Total phenytoin concentrations were 6.8 +/- 1.8 mcg/ml for the head trauma patients and 14.5 +/- 3.0 mcg/ml for the epileptic patients (p less than 0.0002) even though phenytoin doses were similar. However, unbound phenytoin concentrations were within the therapeutic range of 1 to 2 mcg/ml for both groups and were not significantly different. Had only the total concentrations been measured, phenytoin doses might have been increased inappropriately in the head trauma patients. The reason head trauma patients had therapeutic unbound concentrations despite lower total concentrations was that the unbound per cent of phenytoin was higher in these patients (21 +/- 3.2%) than in the epileptic patients (10 +/- 1.3%, p less than 0.0002).