Dilantin, Phenytek

Renal impairment

Less than 5% of phenytoin is cleared by renal clearance.39 Nevertheless, renal impairment has significant effects on phenytoin pharmacokinetics. Because of decreased protein binding in renal failure, the following occur:61

  • decreased total phenytoin plasma concentration
  • no change in free phenytoin concentration, because hepatic metabolism is unchanged
  • increase in free fraction of phenytoin

These changes can lead to overdosing of phenytoin if the dosing rate is based upon the total phenytoin plasma concentration. Monitoring of the free phenytoin plasma concentration is preferred in patients with renal insufficiency.


Phenytoin is poorly soluble in water, is 90% protein bound, and has a modest volume of distribution. As predicted, little phenytoin (2% to 4%) is lost in hemodialysis,62 peritoneal dialysis,63 or continuous ambulatory peritoneal dialysis.64 In a patient undergoing plasmapheresis, 10% of total phenytoin was removed with each treatment.65

Adapted from: Browne TR. Renal disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;49-62.
With permission from Elsevier (www.elsevier.com). 

Authored By: 
TR Browne
Steven C. Schachter, MD
Authored Date: 
Reviewed By: 
Steven C. Schachter, MD
Saturday, January 31, 2004