Corrected Phenytoin Calculator (Sheiner-Tozer)
Corrected Phenytoin Calculator (Sheiner-Tozer)
Correct a total phenytoin level for hypoalbuminaemia using the Sheiner-Tozer equation, so a low albumin does not mask a therapeutic free level.
Corrected Phenytoin (Sheiner-Tozer)
Albumin correctionMeasured total phenytoin 8.5 µg/mL, albumin 2.4 g/dL
Formula
- 0.2 × alb + 0.1
- the denominator equals 0.98 at an albumin of 4.4 g/dL, so the equation is normalised to 4.4 rather than 4.0 — at an albumin of 4.0 it still returns about 1.11 times the measured value
- measured
- measured total phenytoin, µg/mL (numerically the same as mg/L)
- albumin
- serum albumin, g/dL
- 0.2
- reflects the fraction of phenytoin normally bound to albumin, about 90%, scaled per g/dL
- 0.1
- a fixed term for binding that does not depend on albumin concentration
Worked example
Measured total phenytoin 8.5 µg/mL, albumin 2.4 g/dL
0.2 × 2.4 + 0.1 = 0.58
8.5 ÷ 0.58 = 14.7 µg/mL corrected
The uncorrected total of 8.5 µg/mL looked subtherapeutic; corrected for albumin it sits within the therapeutic range
Phenytoin reference ranges
| Measure | Range |
|---|---|
| Total phenytoin | 10 – 20 µg/mL |
| Free phenytoin | 1 – 2 µg/mL |
| Free fraction, normal albumin | about 10% |
| µg/mL to µmol/L | multiply by 3.96 |
Why a normal albumin assumption goes wrong
Phenytoin circulates about 90% bound to albumin, and only the unbound 10% crosses into tissue and produces its anticonvulsant and toxic effects alike. A standard immunoassay measures total phenytoin — bound plus free — on the implicit assumption that a patient’s albumin, and therefore their bound fraction, is normal. When albumin falls, less drug is bound, the free fraction rises, and a total level that looks subtherapeutic can conceal a free concentration that is already therapeutic or even toxic.
The Sheiner-Tozer equation adjusts for this by estimating what the total level would read if albumin were normal, using an empirically derived coefficient for the albumin-bound fraction. It performs reasonably across the everyday range of hypoalbuminaemia seen on general wards, but it is an approximation drawn from a small dataset, it does not account for other displacing factors — uraemia or other highly protein-bound drugs — and its error grows at the extremes of albumin.
Where a free phenytoin assay is available, use it directly rather than relying on the correction; it removes the guesswork the equation exists to manage. Reserve this calculator for the common situation where only a total level and an albumin are on hand and a bedside estimate is needed before the free assay result returns. Note that patients with significant renal failure need the separate, more aggressive correction, because uraemic toxins displace phenytoin from albumin beyond what hypoalbuminaemia alone explains.
Frequently asked questions
Why does the correction change my result even when albumin is normal?
Because the equation is normalised to an albumin of 4.4 g/dL, not 4.0. At 4.4 the denominator is 0.98 and the corrected value is essentially the measured one; at 4.0 it is 0.9, so the equation returns about 11% more than you measured. Treat a small correction at a near-normal albumin as noise rather than a real difference.
Why correct a phenytoin level for albumin?
Because only the free (unbound) fraction is pharmacologically active, and phenytoin is normally about 90% bound to albumin. A low albumin raises the free fraction, so a total level that looks subtherapeutic may already be therapeutic or toxic.
What is the therapeutic range?
10-20 µg/mL for total phenytoin, or 1-2 µg/mL for free phenytoin measured directly. µg/mL and mg/L are the same unit; multiply by 3.96 to convert to µmol/L.
Is the corrected value as reliable as a measured free level?
No. The Sheiner-Tozer equation is a population estimate derived from a small dataset, and its accuracy falls at very low albumin or when other protein-binding interactions are present. Where a free phenytoin assay is available, use it directly.
Should I use this equation in a patient with renal failure?
No — use the separate renal failure correction instead. Uraemic toxins displace phenytoin from albumin further than hypoalbuminaemia alone, so this standard coefficient under-corrects in that setting.
Related calculators
References
- Sheiner LB, Tozer TN. Clinical pharmacokinetics of phenytoin. In: Melmon KL, Morrelli HF, eds. Clinical Pharmacology: Basic Principles in Therapeutics. Macmillan; 1976.
- Winter ME. Basic Clinical Pharmacokinetics, 6th ed. Lippincott Williams & Wilkins.