A 60-year-old female with a history of epilepsy presents to the emergency department with complaints of multiple seizures in the last 24 hours. She is currently taking phenytoin 400 mg once daily. Her total phenytoin level is 30 mcg/mL, and her albumin level is 2.8 g/dL. Her latest Chem-7 showed normal renal function. The healthcare provider wants to assess the patient's free phenytoin level and corrected phenytoin level to determine if her seizures are related to subtherapeutic or toxic levels of phenytoin.

If phenytoin is 90% protein-bound, what is the patient's free phenytoin level, and what is their corrected phenytoin level?

A) Free phenytoin level is 3 mcg/mL, corrected phenytoin level is 39.62 mcg/mL.

B) Free phenytoin level is 3.3 mcg/mL, corrected phenytoin level is 52.38 mcg/mL.

C) Free phenytoin level is 3 mcg/mL, corrected phenytoin level is 45.45 mcg/mL.

D) Free phenytoin level is 4.5 mcg/mL, corrected phenytoin level is 62.50 mcg/mL.

Answer with rationale:

Phenytoin (Dilantin) is one of the most difficult drugs in clinical practice to dose primarily due to its unique kinetics. It is called by a number of different names including Michaelis–Menten, zero order, or even saturable metabolism. All of these mean the same thing clinically: dosing for phenytoin is non-linear. Small changes in dosing can give significantly greater changes in concentration which can result in toxicity. Voriconazole (Vfend) is another medication that follows nonlinear kinetics. 

Steps to determine the answer

To calculate the patient's free phenytoin level, we multiply the total phenytoin level by the fraction unbound, which is 10% since phenytoin is 90% protein-bound.

Free phenytoin level = Total phenytoin level x (fraction unbound) = 30 mcg/mL x 0.10 = 3 mcg/mL

To calculate the patient's corrected phenytoin level, there are a number of formulas sometimes used, but most use this formula for patients with normal renal function:

Corrected phenytoin level = Total phenytoin level ÷ (0.2 x albumin level + 0.1)

Corrected phenytoin level = 30 mcg/mL ÷ (0.2 x 2.8 + 0.1) = 30 mcg/mL ÷ (0.56 + 0.1) = 30 mcg/mL ÷ 0.66 = 45.45 mcg/mL

Therefore, the patient's free phenytoin level is 3 mcg/mL, and their corrected phenytoin level is 45.45 mcg/mL. Goal serum concentration for total phenytoin is 10-20 mcg/ml and a free phenytoin serum concentration of 1-2 mcg/ml. You can obtain a free phenytoin concentration from a blood draw as well but many times this lab is not available locally and must be sent out to determine. These levels indicate that the patient's phenytoin level is elevated and may be contributing to her seizures due to toxic concentrations. Other signs and symptoms of phenytoin toxicity include ataxia, slurred speech, nausea, vomiting, and the classic toxicity sign of nystagmus.  The healthcare provider may consider adjusting the patient's medication dose or adding a second medication to address the subtherapeutic level.

NAPLEX competencies Covered

• 4.1 – Patient parameters or laboratory measures
• 4.5 – Drug concentrations, ratio strengths, osmolarity, osmolality, or extent of ionization

May is here! Are you getting more confidence each week? Keep up the work and you will be prepared soon enough!

Dr. B