Corrected Phenytoin (Sheiner-Tozer)

Background

The Sheiner-Tozer equation corrects a measured total phenytoin level for low albumin, because phenytoin is highly protein-bound and only the free (unbound) fraction is pharmacologically active. When albumin is low, more drug is unbound, so a total level may appear deceptively normal or low while the effective concentration is higher. The standard formula divides the measured level by a factor based on albumin, conventionally (0.2 × albumin in g/dL + 0.1), to estimate what the total level would be at normal albumin. A separate renal variant is used when there is significant impairment, which further reduces protein binding.

Interpreting the result

The corrected level is interpreted against the usual therapeutic range of about 10–20 mg/L: below 10 mg/L is below the usual target, 10–20 mg/L is the typical therapeutic range, and above 20 mg/L raises the risk of toxicity. The correction often reveals that a low-looking total level is in fact adequate, or that a level appearing within range is actually high in a hypoalbuminaemic patient. The number guides interpretation but should always be weighed against seizure control and signs of toxicity rather than treated as an absolute target.

Worked example

A patient has a measured total phenytoin of 8 mg/L with an albumin of 2.0 g/dL. The correction factor is (0.2 × 2.0 + 0.1) = 0.5, so the corrected level is 8/0.5 = 16 mg/L — within the usual therapeutic range despite the low-looking total value.

Pearls / pitfalls

• Enter albumin in g/dL (divide a g/L value by 10) to match the standard equation.
• Use the renal variant in significant renal impairment, as uraemia further displaces phenytoin from albumin and the standard formula under-corrects.
• A directly measured free (unbound) phenytoin level is more reliable than any correction and is preferred when available.
• Always interpret the corrected level alongside clinical state — seizure control and toxicity signs such as nystagmus or ataxia matter more than the number.

Evidence & validation

The correction derives from the protein-binding pharmacokinetics described by Sheiner and Tozer and remains the standard bedside adjustment in therapeutic drug monitoring, recommended where albumin is low or renal function impaired; a directly measured free phenytoin level is the reference standard where available.

Frequently asked questions

References

1. Sheiner LB, Tozer TN. Clinical pharmacokinetics: the use of plasma concentrations of drugs in patient care. In: Melmon and Morrelli's Clinical Pharmacology. 1978.
2. Winter ME. Basic Clinical Pharmacokinetics. 5th ed. Lippincott Williams & Wilkins; 2010 (phenytoin protein-binding correction).

Related calculators