Phenytoin Correction Calculator
Dilantin correction calculator for hypoalbuminemia
ClinCalc.com » Neurology » Phenytoin (Dilantin) Correction Calculator
RESULTS
Corrected phenytoin level 
13.3 mcg/mL
(goal 10 to 20 mcg/mL)

Estimated free phenytoin level 
1.3 mcg/mL
(assumes 10% protein binding)

Potential range of corrected level
What do these coefficients mean?

$$\\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{Coefficient * Albumin + 0.1}\\ Corrected\;phenytoin = \frac{(11\;mcg/mL)}{0.29 * 2.5 + 0.1} = 13.3\;mcg/mL$$
About This Calculator
Due to its narrow therapeutic index and nonlinear pharmacokinetic profile, phenytoin therapeutic drug monitoring is recommended. Because phenytoin is highly protein bound and only unbound drug is capable of crossing the bloodbrain barrier to exert its pharmacologic effect, unbound (free) phenytoin levels may be more clinically relevant than total levels to maximize efficacy and minimize toxicity.^{1}^{,}^{2}
Although unbound (free) phenytoin levels can be measured by a laboratory assay, this method may not be available onsite at all institutions, or the turnaround time for a result may be so long that it limits its clinical utility. The WinterTozer equation was developed to help clinicians estimate an unbound (free) phenytoin concentration based on a total phenytoin level and a serum albumin level.
Corrected Total Phenytoin Level
In patients with hypoalbuminemia, a corrected equation must be used to account for reduced phenytoin protein binding. This calculator uses the following revised WinterTozer correction equation, which was validated in a neurosurgical intensive care unit patient population. Note that this equation is a variant of the traditional WinterTozer equation, which has been demonstrated to be less accurate.^{3}
$$\\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{0.29 * Albumin + 0.1}$$
For those with significant uremia (CrCl < 10 mL/min or hemodialysis), an alternative correction equation is used:^{4}
$$\\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{0.1 * Albumin + 0.1}$$
Traditional WinterTozer Equation
The original WinterTozer equation^{4} (displayed below) was initially developed in patients with epilepsy assuming a normal serum albumin of 4.4 g/dL and a free fraction of 10%. By simplifying the equation, a coefficient of '0.2' was originally suggested to calculate a corrected phenytoin level in patients without significant comorbidities.^{5} In patients with renal dysfunction or endstage renal disease, a coefficient of '0.1' is considered to be more appropriate due to reduced protein binding secondary to uremia, although this method has been shown to poorly correlated with free phenytoin levels.^{4}^{,}^{6}
$$
\\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{\frac{Albumin}{4.4}*0.9+0.1}
\\
\\
\\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{0.2 * Albumin + 0.1}
\\
\\ Renal\;dysfunction:
\\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{0.1 * Albumin + 0.1}
$$
Inaccuracies of the Traditional WinterTozer Equation
There is considerable controversy regarding the accuracy of the traditional WinterTozer equation. As previously mentioned, the traditional WinterTozer equation has repeatedly been shown to overpredict corrected phenytoin levels.^{6} At least two equations, using a coefficient of 0.25 or 0.29, have been suggested to improve the accuracy of a corrected phenytoin level.^{3}^{,}^{7} Despite the preponderance of data against the traditional WinterTozer equation, recent articles still support its use, particularly if the phenytoin assay is run at body temperature (not room temperature).^{8}
Correction Factors for this Calculator
On the basis of available literature, the following coefficients are provided by this clinical calculator:
0.1 
Suggested for endstage renal disease patients  likely inaccurate 
^{4}^{,}^{6} 
0.2 
Traditional (original) WinterTozer equation  likely inaccurate for laboratories that run the phenytoin assay at room temperature 
^{4}^{,}^{8}^{,}^{1}^{,}^{2} 
0.25 
Revised WinterTozer equation studied in elderly patients and severe head trauma; significantly more accurate than the traditional equation 
^{7} 
0.29 
Revised WinterTozer equation studied in neurointensive care unit patients; significantly more accurate than the traditional equation 
^{3} 
References and Additional Reading
 May TW, Rambeck B, Jürges U, et al. Comparison of total and free phenytoin serum concentrations measured by highperformance liquid chromatography and standard TDx assay: implications for the prediction of free phenytoin serum concentrations. Ther Drug Monit. 1998;20(6):61923. PMID 9853976.
 Soldin SJ. Free drug measurements. When and why? An overview. Arch Pathol Lab Med. 1999;123(9):8223. PMID 10458831.
 Kane SP, Bress AP, Tesoro EP. Characterization of unbound phenytoin concentrations in neurointensive care unit patients using a revised WinterTozer equation. Ann Pharmacother. 2013;47(5):62836. PMID 23606554.
 Winter MG, Tozer TN. Chapter 25. Phenytoin. In: Evans WE, Schentag JJ, Jusko WJ. Applied pharmacokinetics: principles of therapeutic drug monitoring. 3rd ed. Vancouver, WA: Applied Therapeutics, 1992:144.
 Hong JM, Choi YC, Kim WJ. Differences between the measured and calculated free serum phenytoin concentrations in epileptic patients. Yonsei Med J. 2009;50(4):51720. PMID 19718399.
 Mauro LS, Mauro VF, Bachmann KA, et al. Accuracy of two equations in determining normalized phenytoin concentrations. DICP. 1989;23(1):648. PMID 2718487.
 Anderson GD, Pak C, Doane KW, et al. Revised WinterTozer equation for normalized phenytoin concentrations in trauma and elderly patients with hypoalbuminemia. Ann Pharmacother. 1997;31(3):27984. PMID 9066931.
 Mlynarek ME, Peterson EL, Zarowitz BJ. Predicting unbound phenytoin concentrations in the critically ill neurosurgical patient. Ann Pharmacother. 1996;30(3):21923. PMID 8833553.