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

Javadi, Seyyede-Sareh; Mahjub, Reza; Taher, Abbas; Mohammadi, Younes; Mehrpooya, Maryam

doi:10.2147/cpaa.s186322

Cited by 10 publications

(15 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 27 , 28 Application of the Sheiner–Tozer equation, a model presumably driven by a single-factor albumin, may provide inaccurate calculated free phenytoin concentrations. 29 – 31 …”

Section: Discussionmentioning

confidence: 99%

Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations

Wilfred¹,

Mathew²,

Chacko³

et al. 2022

Indian Journal of Critical Care Medicine

View full text Add to dashboard Cite

A bstract Background In critically ill patients with low albumin, dose individualization of phenytoin is a challenge. The currently used Sheiner–Tozer equation does not accurately predict the free phenytoin concentration in serum and can result in incorrect dose modifications. The best measure to advocate in these patients is the direct-measurement of free phenytoin concentration. Aims and objectives Phenytoin exhibits complex pharmacokinetics, requiring careful therapeutic drug monitoring. This study aimed to compare the accuracy of the established Sheiner–Tozer calculation method against the direct-measurement of free phenytoin concentration in serum by high performance liquid chromatography in critically ill patients with low albumin. Materials and methods Blood specimens for direct-measurement of both total and free phenytoin concentration were obtained from 57 patients with hypoalbuminemia monitored in the intensive care unit. Results The median [inter-quartile range (IQR)] for Sheiner–Tozer equation calculated total phenytoin concentration and direct-measured total was 17.14 (10.63–24.53) and 9.82 (6.02–13.85) μg mL −1 , respectively. Approximately 53 and 5% of patients were found to be subtherapeutic and supratherapeutic for direct-measured total phenytoin concentrations, respectively. In contrast, on applying the Sheiner–Tozer calculation, 23 and 40% had subtherapeutic and supratherapeutic concentrations, respectively, for total phenytoin concentration. The median (IQR) for direct-measured, routine and Sheiner–Tozer equation calculated free phenytoin concentration were 1.92 (1.06–2.76), 0.98 (0.60–1.39), and 1.71 (1.06–2.45) μg mL −1 , respectively. Only 45.7% of patients were in agreement with respect to the therapeutic category when direct-measured free was compared against routine calculation free. Conclusion In patients with low albumin, free phenytoin concentration based on the Sheiner–Tozer corrected equation accurately classified patients based on their therapeutic category of free phenytoin in 73.7% of patients. Hence, for individualization of phenytoin dosage in critically ill patients with low albumin, we recommend direct-measurement of free phenytoin concentration. How to cite this article Wilfred PM, Mathew S, Chacko B, Prabha R, Mathew BS. Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations. Indian J Crit Care Med 2022;26(6):682–687.

show abstract

“… 27 , 28 Application of the Sheiner–Tozer equation, a model presumably driven by a single-factor albumin, may provide inaccurate calculated free phenytoin concentrations. 29 – 31 …”

Section: Discussionmentioning

confidence: 99%

Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations

Wilfred¹,

Mathew²,

Chacko³

et al. 2022

Indian Journal of Critical Care Medicine

View full text Add to dashboard Cite

show abstract

“…An example reporting a complete evaluation of ASMs plasma levels is given by Patsalos and coworkers, who developed an LC-MS method to measure both free and total concentration of 25 different ASMs in a single run [ 27 ]. Conversely, many methods were set up to measure the free fraction of a single drug; in particular, most of them are focused on the analysis of PHT and VPA by HPLC-UV, LC-MS/MS [ 56 , 57 , 58 ], or GC techniques [ 59 ].…”

Section: Analytical Tools For the Evaluation Of Asms’ Free Drug Fractionmentioning

confidence: 99%

The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

et al. 2021

View full text Add to dashboard Cite

Epilepsy is a widely diffused neurological disorder including a heterogeneous range of syndromes with different aetiology, severity and prognosis. Pharmacological treatments are based on the use, either in mono- or in polytherapy, of antiseizure medications (ASMs), which act at different synaptic levels, generally modifying the excitatory and/or inhibitory response through different action mechanisms. To reduce the risk of adverse effects and drug interactions, ASMs levels should be closely evaluated in biological fluids performing an appropriate Therapeutic Drug Monitoring (TDM). However, many decisions in TDM are based on the determination of the total drug concentration although measurement of the free fraction, which is not bound to plasma proteins, is becoming of ever-increasing importance since it correlates better with pharmacological and toxicological effects. Aim of this work has been to review methodological aspects concerning the evaluation of the free plasmatic fraction of some ASMs, focusing on the effect and the clinical significance that drug-protein binding has in the case of widely used drugs such as valproic acid, phenytoin, perampanel and carbamazepine. Although several validated methodologies are currently available which are effective in separating and quantifying the different forms of a drug, prospective validation studies are undoubtedly needed to better correlate, in real-world clinical contexts, pharmacokinetic monitoring to clinical outcomes.

show abstract

Section: Serum Albumin Levels For Therapeutic Drug Monitoringmentioning

confidence: 99%

“…Similarly, all the studies evaluating phenytoin correction equations since the comprehensive review have concluded that monitoring of free concentrations are preferred in critically ill patients. [15][16][17] Valproate is similar to phenytoin in that it has approximately 90% binding to albumin and 10% of the free form in plasma. In contrast to phenytoin, there are no equations commonly used in the clinical setting for adjusting valproate levels based on serum albumin levels.…”

Section: Serum Albumin Levels For Therapeutic Drug Monitoringmentioning

confidence: 99%

Serum Albumin Levels: Who Needs Them?

Erstad

2020

Ann Pharmacother

View full text Add to dashboard Cite

Objectives The purpose of this critical narrative review is to discuss common indications for ordering serum albumin levels in adult critically ill patients, evaluate the literature supporting these indications, and provide recommendations for the appropriate ordering of serum albumin levels. Data Sources PubMed (1966 to August 2020), Cochrane Library, and current clinical practice guidelines were used, and bibliographies of retrieved articles were searched for additional articles. Study Selection and Data Extraction Current clinical practice guidelines were the preferred source of recommendations regarding serum albumin levels for guiding albumin administration and for nutritional monitoring. When current comprehensive reviews were available, they served as a baseline information with supplementation by subsequent studies. Data Synthesis Serum albumin is a general marker of severity of illness, and hypoalbuminemia is associated with poor patient outcome, but albumin is an acute phase protein, so levels vacillate in critically ill patients in conjunction with illness fluctuations. The most common reasons for ordering serum albumin levels in intensive care unit (ICU) settings are to guide albumin administration, to estimate free phenytoin or calcium levels, for nutritional monitoring, and for severity-of-illness assessment. Relevance to Patient Care and Clinical Practice Because hypoalbuminemia is common in the ICU setting, inappropriate ordering of serum albumin levels may lead to unnecessary albumin administration or excessive macronutrient administration in nutritional regimens, leading to possible adverse effects and added costs. Conclusions With the exception of the need to order serum albumin levels as a component of selected severity-of-illness scoring systems, there is little evidence or justification for routinely ordering levels in critically ill patients.

show abstract

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

Cited by 10 publications

References 31 publications

Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations

Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations

The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

Serum Albumin Levels: Who Needs Them?

Contact Info

Product

Resources

About