TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: PNYF    
Phenytoin, Free, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring for appropriate therapeutic concentration of free phenytoin: free phenytoin level is the best indicator of adequate therapy in renal failure

 

Assessing compliance and toxicity

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Phenytoin is the drug of choice to treat and prevent tonic-clonic and psychomotor seizures. If phenytoin alone will not prevent seizure activity, coadministration with phenobarbital is usually effective.
Phenytoin is highly protein-bound (90%), mostly to albumin. Ten percent of the phenytoin circulates in the free, unbound form. Free phenytoin is the active form of the drug, available to cross biologic membranes and bind to receptors. Increased free phenytoin produces an enhanced pharmacologic effect. At the same time, the free fraction is more available to the liver to be metabolized, so it is cleared more quickly.
Concurrent use of phenytoin and valproic acid (another frequently used antiepileptic) may result in altered valproic acid levels and/or altered phenytoin levels. Due to the complex situation involving displacement of protein-bound phenytoin and inhibition of phenytoin metabolism, as well as the potential for decreased valproic acid concentrations, patients should be monitored for both phenytoin toxicity and therapeutic efficacy. Free phenytoin levels should be measured to provide the most accurate assessment of phenytoin activity early in therapy. At steady-state, free phenytoin and free valproic acid concentrations should be normalized.
In renal failure, the opportunity for the free phenytoin fraction to be cleared is significantly reduced. The end result is that both the total and free concentration of phenytoin increase, with the free concentration increasing faster than the total. Dosage must be reduced to avoid toxicity. Accordingly, the free phenytoin level is the best indicator of adequate therapy in renal failure.
Toxicity is a constant possibility because of the manner in which phenytoin is metabolized. Small increases in dose can lead to very large increases in blood concentration, resulting in early signs of toxicity such as nystagmus, ataxia, and dysarthria. Severe toxicity is typified by tremor, hyperreflexia, lethargy, and coma.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Therapeutic: 1.0-2.0 mcg/mL Critical value: > or =2.5 mcg/mL

Interpretation Provides information to assist in interpretation of the test results

Dose should be adjusted to achieve steady-state blood concentration of free phenytoin between 1.0 and 2.0 mcg/mL. The range for percent free phenytoin is 8% to 14%.

 

Severe toxicity occurs when the free phenytoin concentration is > or =2.5 mcg/mL. However, response and side effects will be individual.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

No significant cautionary statements

Clinical Reference Recommendations for in-depth reading of a clinical nature

Richens A: Clinical pharmacokinetics of phenytoin. Clin Pharmacokinet 1979;4:153-169