Phenytoin (Dilantin) Correction for Albumin and Renal Failure
Normal range: 3.5-5.0 g/dL
What is Phenytoin Correction?
Phenytoin (Dilantin) is an antiepileptic drug that is highly protein-bound, primarily to albumin. In patients with hypoalbuminemia (low albumin levels), there is an increase in the free (unbound) fraction of phenytoin, which is the pharmacologically active component. Standard laboratory tests measure the total phenytoin concentration (both bound and unbound), which can lead to misleading results in patients with low albumin levels.
The Sheiner-Tozer equation is used to estimate the corrected phenytoin level in patients with hypoalbuminemia, providing a more accurate representation of the therapeutic effect.
The Sheiner-Tozer Equation
Corrected Phenytoin = Measured Phenytoin / [(0.2 × Albumin) + 0.1]
Where albumin is measured in g/dL
This equation adjusts the measured phenytoin level based on the patient's albumin level, providing an estimate of what the phenytoin level would be if the patient had normal albumin levels (4.4 g/dL).
Clinical Significance
Proper interpretation of phenytoin levels is crucial for effective seizure management. The therapeutic range for total phenytoin concentration is typically 10-20 μg/mL (40-80 μmol/L). In patients with hypoalbuminemia:
- The measured (total) phenytoin level may appear falsely low
- The free (unbound) phenytoin concentration may still be within the therapeutic range
- Dosing based on uncorrected levels may lead to phenytoin toxicity
Using the corrected phenytoin level helps guide appropriate dosing decisions in patients with altered protein binding.
Renal Failure Considerations
In patients with renal failure, there are additional considerations:
- Uremic toxins can displace phenytoin from albumin binding sites
- This further increases the free fraction of phenytoin
- For patients with renal failure, a modified equation is sometimes used that incorporates both albumin and creatinine clearance
In severe renal impairment, direct measurement of free phenytoin levels may be preferable when available.
Limitations
The Sheiner-Tozer equation has several limitations:
- It provides an estimate, not an exact measurement of free phenytoin
- It may not account for all factors affecting protein binding
- It doesn't consider displacement of phenytoin by other highly protein-bound drugs
- The equation was developed using specific assay methods that may differ from current laboratory techniques
When available, direct measurement of free phenytoin concentration is the most accurate method for guiding therapy in patients with altered protein binding.
References
- Sheiner LB, Tozer TN. Clinical pharmacokinetics: the use of plasma concentrations of drugs. In: Melmon KL, Morelli HF, eds. Clinical Pharmacology: Basic Principles in Therapeutics. New York: Macmillan; 1978:71-109.
- Winter ME. Basic Clinical Pharmacokinetics. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.
- Anderson GD, Pak C, Doane KW, et al. Revised Winter-Tozer equation for normalized phenytoin concentrations in trauma and elderly patients with hypoalbuminemia. Ann Pharmacother. 1997;31(3):279-284.
- Kiang TK, Ensom MH. A qualitative review on the pharmacokinetics of antibiotics in saliva: implications on clinical pharmacokinetic monitoring in humans. Clin Pharmacokinet. 2016;55(3):313-358.