Precision, Bias, and Clinical Utility of the Sheiner‐Tozer Equation to Guide Phenytoin Dosing in Critically Ill Adults

Bolt, Jennifer; Gorman, Sean K

doi:10.1002/jcph.27

Cited by 10 publications

(23 citation statements)

References 17 publications

(42 reference statements)

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“…For example, the Sheiner‐Tozer equation can only reliably be used in patients without clinically significant renal impairment, or in patients who do not receive other drugs that are extensively albumin‐bound. It was shown previously that the prediction of unbound PHY concentration using the Sheiner‐Tozer equation was biased and it significantly underestimated the observed unbound PHY concentrations . We also evaluated the predictive performance, according to Sheiner and Beal of both the Sheiner‐Tozer equation and the present model to predict an individual's unbound phenytoin concentration in the data set.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown previously that the prediction of unbound PHY concentration using the Sheiner-Tozer equation was biased and it significantly underestimated the observed unbound PHY concentrations. 32,33 We also evaluated the predictive performance, according to Sheiner and Beal 34 of both the Sheiner-Tozer equation and the present model to predict an individual's unbound phenytoin concentration in the data set. The relative prediction error and the root mean squared error was 0.3% and 0.15 mg/L for our model, and À21.0% and 0.32 mg/L when using the Sheiner-Tozer equation, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of phenytoin in critically ill children

Hennig

Norris

et al. 2014

The Journal of Clinical Pharma

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The objective was to study the population pharmacokinetics of bound and unbound phenytoin in critically ill children, including influences on the protein binding profile. A population pharmacokinetic approach was used to analyze paired protein-unbound and total phenytoin plasma concentrations (n = 146 each) from 32 critically ill children (0.08-17 years of age) who were admitted to a pediatric hospital, primarily intensive care unit. The pharmacokinetics of unbound and bound phenytoin and the influence of possible influential covariates were modeled and evaluated using visual predictive checks and bootstrapping. The pharmacokinetics of protein-unbound phenytoin was described satisfactorily by a 1-compartment model with first-order absorption in conjunction with a linear partition coefficient parameter to describe the binding of phenytoin to albumin. The partitioning coefficient describing protein binding and distribution to bound phenytoin was estimated to be 8.22. Nonlinear elimination of unbound phenytoin was not supported in this patient group. Weight, allometrically scaled for clearance and volume of distribution for the unbound and bound compartments, and albumin concentration significantly influenced the partition coefficient for protein binding of phenytoin. The population model can be applied to estimate the fraction of unbound phenytoin in critically ill children given an individual's albumin concentration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of phenytoin in critically ill children

Hennig

Norris

et al. 2014

The Journal of Clinical Pharma

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“…Krasowski and Penrod 20 also studied intensive care patients, but because of heterogeneity of their study population (see Table 1), this study will be discussed under Other Populations. Bolt et al 15 analyzed data from 2 separate studies (a subset of Mauro et al 18 and same data as presented in Mlynarek et al, 17 retrospectively). All patients in this group had average albumin <3.5 g/dL, and inconsistencies were evident on the predictive performance of the Sheiner-Tozer equation because significant negative bias with imprecision 12,18 and slightly positive bias with imprecision 17 were reported in different studies when predicted concentrations were compared with measured phenytoin concentrations (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…10 The gold standard Sheiner-Tozer equation (Table 1) uses a corrective coefficient to predict the phenytoin concentration if albumin concentration had been normal. 14,15…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Review on the Predictive Performance of the Sheiner-Tozer and Derivative Equations for the Correction of Phenytoin Concentrations

Kiang

Ensom

2016

Ann Pharmacother

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“…However, there are conflicting results concerning its accuracy and precision for prediction of free phenytoin concentration. Results of several studies have demonstrated that this equation is an inaccurate predictor for phenytoin-dose adjustment in all patients, because in addition to hypoalbuminemia, several other factors, such as renal and liver dysfunction, as well as concomitant-medication consumption, can alter free phenytoin concentration, especially in critically ill patients 16. Considering the impact of these factors on free phenytoin concentration, some studies have used a revised Sheiner–Tozer equation containing different coefficients to improve the accuracy of the equation for prediction of free phenytoin concentration.…”

Section: Introductionmentioning

confidence: 99%

Correlation between measured and calculated free phenytoin serum concentration in neurointensive care patients with hypoalbuminemia

Javadi¹,

Mahjub²,

Taher³

et al. 2018

CPAA

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PurposeIn critically ill patients, monitoring free phenytoin concentration is a valuable method for phenytoin-dosage adjustment. However, due to technical difficulties and the high cost of these methods, the Sheiner–Tozer equation is routinely used for estimating free phenytoin concentration in clinical practice. There have been conflicting results concerning accuracy and precision of the Sheiner–Tozer equation for prediction of free phenytoin concentration in various patient populations. Therefore, this study was conducted to evaluate the accuracy and correlation of measured and calculated free phenytoin concentrations in neurointensive care patients with hypoalbuminemia.MethodsA total of 65 adult neurointensive care patients with hypoalbuminemia who were receiving phenytoin for prevention or treatment of seizures were recruited in this study. In addition to measuring free phenytoin concentration by HPLC, free phenytoin concentration was calculated using both conventional and revised Sheiner–Tozer equations. Eventually, the correlation and level of agreement between measured and calculated free phenytoin concentrations were evaluated.ResultsThe mean albumin concentration of studied patients was 2.63±0.57 g/dL. There was a significant but weak–moderate correlation between measured and calculated free phenytoin concentration using conventional and revised Sheiner–Tozer equations (r=0.45 and r=0.43, respectively). Conventional and revised Sheiner–Tozer equations were not able to predict free phenytoin concentrations accurately in 33.85% and 35.4% of patients, respectively. Although the sex of patients did not have a significant impact on the level of agreement, younger patients had a higher level of agreement.ConclusionAlthough there was a moderate correlation between calculated and measured free phenytoin concentration, the Sheiner–Tozer equation was not able to predict free phenytoin concentration accurately in all patients, especially in older patients. Therefore, monitoring free phenytoin serum concentration besides clinical outcomes should be considered for phenytoin-dose adjustment in critically ill patients.

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Precision, Bias, and Clinical Utility of the Sheiner‐Tozer Equation to Guide Phenytoin Dosing in Critically Ill Adults

Cited by 10 publications

References 17 publications

Population pharmacokinetics of phenytoin in critically ill children

Population pharmacokinetics of phenytoin in critically ill children

A Comprehensive Review on the Predictive Performance of the Sheiner-Tozer and Derivative Equations for the Correction of Phenytoin Concentrations

Correlation between measured and calculated free phenytoin serum concentration in neurointensive care patients with hypoalbuminemia

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