• Phenytoin has a wide volume of distribtuion and is 90% bound to protein. 
• Only the unbound proportion is biologically active, and therefore, FREE levels of phenytoin should be checked to determine whether acute seizure activity is related to suboptimal levels or not. 
• Given these properties, patients with the following conditions are more likely to become phenytoin toxic:  neonates and the elderly (due to poor metabolism and low protein production); uremia, nephrotic syndrome, pregnancy, malignancy, malnutrition (due to low potein levels).

References