Corrected Phenytoin in Renal Failure
Corrected Phenytoin in Renal Failure
Correct a total phenytoin level in patients with a creatinine clearance below 20 mL/min, where uraemia displaces phenytoin from albumin more than hypoalbuminaemia alone.
Corrected Phenytoin in Renal Failure
Renal correctionMeasured total phenytoin 6.0 µg/mL, albumin 3.0 g/dL, creatinine clearance below 20 mL/min
Formula
- measured
- measured total phenytoin, µg/mL
- albumin
- serum albumin, g/dL
- 0.1 (albumin term)
- half the standard coefficient — uraemic toxins reduce albumin binding beyond what hypoalbuminaemia alone explains
- when to use
- creatinine clearance below about 20 mL/min, including patients on dialysis
Worked example
Measured total phenytoin 6.0 µg/mL, albumin 3.0 g/dL, creatinine clearance below 20 mL/min
0.1 × 3.0 + 0.1 = 0.4
6.0 ÷ 0.4 = 15.0 µg/mL corrected
The standard Sheiner-Tozer equation with the same inputs gives 6.0 ÷ 0.7 = 8.6 µg/mL — a clinically important difference
Choosing the equation
| Creatinine clearance | Equation | Albumin coefficient |
|---|---|---|
| 20 mL/min or above | Standard Sheiner-Tozer | 0.2 |
| Below 20 mL/min, including dialysis | Renal failure correction | 0.1 |
Why the coefficient halves in renal failure
In advanced renal failure, accumulated uraemic toxins compete with phenytoin for albumin binding sites, on top of whatever hypoalbuminaemia is already present. The result is a bound fraction that falls further than the albumin concentration alone would predict, so the standard Sheiner-Tozer coefficient — derived in patients without significant renal impairment — under-corrects in this population.
The renal failure variant halves the albumin coefficient, from 0.2 to 0.1, reflecting this additional displacement. Applied to the same total level and albumin, it returns a higher corrected concentration than the standard equation, because it assumes a smaller bound fraction. Using the standard equation in a dialysis patient systematically underestimates the true corrected level and risks an unnecessary dose increase in a patient who may already be adequately, or even excessively, treated.
The equation to use is decided by creatinine clearance, not by the albumin value: below roughly 20 mL/min, including patients on dialysis, use this correction regardless of whether albumin is itself low or normal. As with the standard correction, this remains an estimate — where a free phenytoin assay is available, particularly in a patient with both renal failure and hypoalbuminaemia, it is the more reliable result.
Frequently asked questions
When should I use the renal failure phenytoin correction?
When creatinine clearance is below about 20 mL/min, including patients on dialysis. Uraemic toxins displace phenytoin from albumin beyond what hypoalbuminaemia alone accounts for, so the standard equation under-corrects.
How does this equation differ from the standard Sheiner-Tozer equation?
Only the albumin coefficient changes, from 0.2 to 0.1, reflecting the further loss of protein binding caused by uraemic toxins. The structure of the equation is otherwise identical.
Is the choice of equation based on albumin or renal function?
Renal function. A patient with a low creatinine clearance needs this equation even if their albumin happens to be normal, because the displacement is driven by uraemic toxins rather than by albumin concentration alone.
Is this correction as accurate as a measured free phenytoin level?
No — like the standard correction, it is a population estimate. It is a better estimate than the standard equation in renal failure, but a directly measured free level remains more reliable when available.
Related calculators
References
- Liponi DF, Winter ME, Tozer TN. Renal function and therapeutic concentrations of phenytoin. Neurology. 1984;34(3):395-397.
- Winter ME. Basic Clinical Pharmacokinetics, 6th ed. Lippincott Williams & Wilkins.