Free phenytoin toxicity

Imam, Syed Haider; Landry, Kristen; Kaul, Viren; Gambhir, Harvir Singh; John, D. H. St; Kloss, Brian T.

doi:10.1016/j.ajem.2014.03.036

Cited by 14 publications

(7 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phenytoin is a state‐dependent sodium channel blocker with a small preference (~10%) for persistent current over peak current . However, high‐dose phenytoin has significant safety concerns due to saturable metabolism and risk for phenytoin poisoning . GS‐458967 (GS967) is a novel sodium channel modulator specifically developed to inhibit persistent sodium current, with a 42‐fold preference for persistent as opposed to peak current inhibition .…”

Section: Introductionmentioning

confidence: 99%

“…17 However, high-dose phenytoin has significant safety concerns due to saturable metabolism and risk for phenytoin poisoning. [18][19][20][21] GS-458967 (GS967) is a novel sodium channel modulator specifically developed to inhibit persistent sodium current, with a 42-fold preference for persistent as opposed to peak current inhibition. 22 Our previous studies demonstrated that acute application of GS967 to hippocampal neurons did not affect the current-voltage relationship or voltage dependence of activation, but induced a hyperpolarized shift of steady-state channel inactivation and slowed both recovery from fast inactivation and onset of slow inactivation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The novel sodium channel modulator GS‐458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy

Thompson

Hawkins

et al. 2018

Epilepsia

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The novel sodium channel modulator GS‐458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy

Thompson

Hawkins

et al. 2018

Epilepsia

View full text Add to dashboard Cite

show abstract

“…Despite its extensive use, phenytoin has a narrow therapeutic index, which requires attention. Toxicological effects include nystagmus, loss of smooth pursuit and eventually coma [17]. Given these disadvantages, the development of a new improved drug is important to reduce such problems.…”

Section: Introductionmentioning

confidence: 99%

Antinociceptive Effect of Hydantoin 3-Phenyl-5-(4-ethylphenyl)-imidazolidine-2,4-dione in Mice

et al. 2015

View full text Add to dashboard Cite

Imidazolidine derivatives, or hydantoins, are synthetic compounds with different therapeutic applications. Many imidazolidine derivatives have psychopharmacological properties, such as phenytoin, famous for its anticonvulsant efficacy, but also effective in the treatment of neuropathic pain. The hydantoin, 3-phenyl-5-(4-ethylphenyl)-imidazolidine-2,4-dione (IM-3), synthesized from the amino acid, glycine, was selected for psychopharmacological studies in mice on the basis of its chemical and structural similarity with phenytoin. The first step of this study was to define the LD50, which determined the doses of 50, 100 and 200 mg/kg for subsequent tests. The results obtained from the behavioral screening indicated that IM-3 produces decreased ambulation and analgesia in mice. Motor coordination and anxiety behavior were not affected by treatment with IM-3, as observed in the rotarod and elevated plus-maze tests, respectively. Regarding its antinociceptive properties, IM-3 showed efficacy in the acetic acid-induced writhing test by OPEN ACCESSMolecules 2015, 20 975 increasing the latency of the first writhe and reducing the number of writhes, as well as reducing the paw licking time in the second phase of the formalin test. The behavior of treated animals exposed to the hot plate test, however, did not differ from that of the control group. These data suggest that IM-3 has antinociceptive effects in mice, which is probably mediated by anti-inflammatory mechanisms.

show abstract

“…The challenge faced by the clinician when treating patients with phenytoin is primarily related to “vital dosing decisions,” to be made in the critical care setting. 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

Free phenytoin toxicity

Cited by 14 publications

References 5 publications

The novel sodium channel modulator GS‐458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy

The novel sodium channel modulator GS‐458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy

Antinociceptive Effect of Hydantoin 3-Phenyl-5-(4-ethylphenyl)-imidazolidine-2,4-dione in Mice

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

Contact Info

Product

Resources

About