Wednesday June 10, 2009
Therapeutic monitoring: Total phenytoin vs Free Phenytoin levels in Critical Care

Phenytoin remains one of the most frequently used medications in critical care to treat various seizure disorders, which also require close therapeutic monitoring to prevent toxicity.

Therapeutic range:

• Total 10-20 mcg/ml;
• Free 1-2 mcg/ml

Phenytoin is 90% protein bound. In critical illness, protein synthesis and binding affinity are altered for various reasons including decreased dietary intake, renal/hepatic impairment, and a catabolic state. Also, critically ill patients have numerous drug-drug and drug-food interactions. In these situations, free phenytoin levels may increase by 2-3 fold, potentially resulting in toxicity. Therefore, the monitoring of free phenytoin levels, not total levels, are the most accurate and strongly correlated with clinical toxicity in critical care.


Reference:

1. Von Winckelmann, SL. Pharmacotherapy 2008;28:1391

2. Evidence-based Implementation of Free Phenytoin therapeutic Drug Monitoring - Clinical Chemistry 46: 1132-1135, 2000