Background: Phenytoin has a narrow therapeutic index and the potential of under-treatment or toxicity. Available equations are used to correct for the impact of hypoalbuminemia on unbound (free) phenytoin levels. The authors aimed to determine the accuracy of equations used to estimate free phenytoin in hospitalized patients and assess the impact of using additional clinical data.
Methods: Concurrently measured total and free phenytoin levels in hospitalized patients (2014-2018) were retrospectively evaluated, excluding those from patients on renal replacement therapy and valproic acid. Differences between actual and estimated free phenytoin levels by the original (Original WTZ), Anderson-modified, and Kane-modified Winter-Tozer equations were assessed using Pearson correlations and Bland-Altman analysis. Thereafter, a population-derived formula was developed and validated in a testing cohort.
Results: In the 4-year training cohort (n = 81), the Original WTZ equation had the smallest mean difference of all equations. A higher mean difference [-0.362 mcg/mL (95% CI -0.585 to -0.138) vs. -0.054 mcg/mL (95% CI -0.186 to 0.078)] was observed in intensive care unit (ICU) patients compared with non-ICU patients. A cross-validated multivariable model improved the accuracy of free phenytoin estimation in ICU and non-ICU patients, even in the separate testing cohort (n = 52) with respective mean differences of -0.322 mcg/mL (95% CI -0.545 to -0.098) and -0.025 mcg/mL (95% CI -0.379 to 0.329) and was superior to the Original WTZ [mean difference -0.858 mcg/mL (95% CI -1.069 to -0.647) vs. -0.106 mcg/mL (95% CI -0.362 to 0.151), respectively].
Conclusions: Free phenytoin levels in hospitalized patients cannot be accurately determined using available estimation equations, particularly in critically ill patients. Combining ICU status and other available clinical data can improve therapeutic drug monitoring and prevent high-magnitude errors, particularly when free phenytoin assays are not readily available.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377971 | PMC |
| http://dx.doi.org/10.1097/FTD.0000000000000739 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Guidelines for Seizure Prophylaxis in Patients Hospitalized with Nontraumatic Intracerebral Hemorrhage: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society.
Neurocrit Care
December 2024
Department of Clinical Pharmacology, University of Tennessee Health Science Center College of Pharmacy, Knoxville, TN, USA.
Background: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASM) in patients hospitalized with acute nontraumatic intracerebral hemorrhage (ICH).
Methods: We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized with acute nontraumatic ICH. The following population, intervention, comparison, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used in patients with acute ICH with no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? and (3) If an ASM is used, should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes assessed were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes.
A Prospective Cohort Study on the Effect of Antiseizure Medications on Thyroid Function in Children Aged 6 Months to 12 Years with Epilepsy.
Sultan Qaboos Univ Med J
November 2024
Department of Pediatrics, Mediclinic City Hospital, Mohammed Bin Rashid University of Medicine & Health Sciences, Dubai, UAE.
Objectives: This study aimed to explore the effect of antiseizure medications (ASM) on thyroid function in children with epilepsy.
Methods: A prospective study involving children between 6 months and 12 years of age with new-onset seizures who took ASM within 2 months was conducted in the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India, between August 2019 to March 2022. Thyroid function tests-free T3, free T4 and thyroid stimulating hormone (TSH)-were done at baseline and after completing 3 months by competitive immunoassay using direct chemiluminescent technology.
New onset seizures in Octogenarians.
Eur Geriatr Med
November 2024
Department of Neurology, R.Madhavan Nayar Center for Comprehensive Epilepsy Care (RMNC), Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum, Kerala, 695 011, India.
Article Synopsis
- New seizures in older adults, especially those over 85, are common, with increased incidence and distinct clinical features as highlighted by a recent study responding to the ILAE task force on epilepsy in the elderly.
- Data from a 30-year epilepsy care center revealed that generalized tonic-clonic seizures were most prevalent among 40 patients, with 50% having unidentified causes, while stroke was the leading known cause.
- Effective treatment was noted with monotherapy controlling seizures in 62.5% of patients, though 47.5% experienced recurrences, often linked to a history of stroke and specific medication use.
Novel microfluidic development of pH-responsive hybrid liposomes: In vitro and in vivo assessment for enhanced wound Healing.
Int J Pharm
December 2024
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral St, Glasgow G4 0RE, UK.
Wound healing is a complex biological process crucial for tissue repair, especially in chronic wounds where healing is impaired. Liposomes have emerged as promising vehicles for delivering therapeutics to facilitate wound repair. Liposomes have been explored as effective carriers for therapeutic agents.
View Article and Find Full Text PDFCerebellar Hypoplasia and Treatment Course of a Two-Month-Old Infant With KCNQ2 Epileptic Encephalopathy Due to a De Novo Variant and Review of the Literature.
Am J Med Genet A
October 2024
Faculty of Medicine, Department of Pediatric Neurology, Gazi University, Ankara, Turkey.
In this paper, we report the treatment course, magnetic resonance imaging (MRI), and electroencephalography (EEG) findings of a two-month-old girl with KCNQ2 epileptic encephalopathy caused by a de novo variant. The patient started having seizures 2 days postnatally. Despite treatment with phenobarbital, phenytoin, levetiracetam, topiramate, clonazepam, vigabatrin, clobazam, and pyridoxine, she continued to have 10 or more seizures per day.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!