ArticleInternational journal of clinical pharmacy2016
Free phenytoin assessment in patients: measured versus calculated blood serum levels.
Article in International journal of clinical pharmacy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Levetiracetam versus phenytoin for seizure prophylaxis in brain injured patients: a systematic review and meta-analysis.International journal of clinical pharmacy · 2017Pooled it
- Effect of hypoalbuminemia on drug pharmacokinetics.Frontiers in pharmacology · 2025Review
- Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2022Article
- Pharmacokinetic Drug-Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients.International journal of molecular sciences · 2021Review
- The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications.Pharmaceutics · 2021Review
- Method for Simultaneous Determination of Free Concentration, Total Concentration, and Plasma Binding Capacity in Clinical Samples.Journal of pharmaceutical sciences · 2021Article
- Evaluation of Fosphenytoin Therapeutic Drug Monitoring in the Neurocritical Care Unit.Drugs in R&D · 2020Article
- Development and Validation of an LC-MS/MS Method and Comparison with a GC-MS Method to Measure Phenytoin in Human Brain Dialysate, Blood, and Saliva.Journal of analytical methods in chemistry · 2018Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTotal serum drug levels are routinely determined for the therapeutic drug monitoring of selected, difficult-to-dose drugs. For some of these drugs, however, knowledge of the free fraction is necessary to adapt correct dosing. Phenytoin, with its non-linear pharmacokinetics, >90 % albumin binding and slow elimination rate, is such a drug requiring individualization in patients, especially if rapid intravenous loading and subsequent dose adaptation is needed. In a prior long-term investigation, we showed the excellent performance of pharmacy-assisted Bayesian forecasting support for optimal dosing in hospitalized patients treated with phenytoin. In a subgroup analysis, we evaluated the suitability of the Sheiner-Tozer algorithm to calculate the free phenytoin fraction in hypoalbuminemic patients.
objectiveTo test the usefulness of the Sheiner-Tozer algorithm for the correct estimation of the free phenytoin concentrations in hospitalized patients.
settingA Swiss tertiary care hospital.
methodFree phenytoin plasma concentration was calculated from total phenytoin concentration in hypoalbuminemic patients and compared with the measured free phenytoin. The patients were separated into a low (35 ≤ albumin ≥ 25 g/L) and a very low group (albumin <25 g/L) for comparing and statistically analyzing the calculated and the measured free phenytoin concentration.
main outcome measuresCalculated and the measured free phenytoin concentration.
resultsThe calculated (1.2 mg/L (SD = 0.7) and the measured (1.1 mg/L (SD = 0.5) free phenytoin concentration correlated. The mean difference in the low and the very low albumin group was: 0.10 mg/L (SD = 1.4) (n = 11) and 0.13 mg/L (SD = 0.24) (n = 12), respectively. Although the variability of the data could be a bias, no statistically significant difference between the groups was found: t test (p = 0.78), the Passing-Bablok regression, the Spearman's rank correlation coefficient of r = 0.907 and p = 0.00. The Bland-Altman plot including the regression analysis revealed no systematic differences between the calculated and the measured value [M = 0.11 (SD = 0.28)].
conclusionIn absence of a free phenytoin plasma concentration measurement also in hypoalbuminemic patients, the Sheiner-Tozer algorithm represents a useful tool to assist therapeutic monitoring to calculate or control free phenytoin by using total phenytoin and the albumin concentration.
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