| Altered phenytoin pharmacokinetics in children with severe, acute traumatic brain injury. | |
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MedLine Citation:
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PMID: 11185666 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The purpose of this study was to determine if phenytoin protein binding and metabolism were altered in prepubescent pediatric patients within the first 10 days following severe, acute traumatic brain injury. Patients (n = 10) received phenytoin loading doses (15-20 mg/kg) followed by a maintenance regimen (7 mg/kg/day) initiated within 12 hours of the loading dose. Phenytoin serum concentrations were measured serially on days 1, 2, 3, 5, 7, 9, and 10 at 1, 6, and 12 hours. Time-invariant and time-variant Michaelis-Menten pharmacokinetic models were fit to the unbound phenytoin concentration-time data (ADAPT II). Albumin concentrations significantly decreased over time (p < 0.001) and were predictive of the phenytoin binding ratio (r2 = 0.373, p < 0.0001). The time-variant model provided a superior fit of the data in 7 patients with no difference between models in 3 patients. Rapid inhibition of metabolism (Vmaxbaseline = 2.82 +/- 2.35 mg/kg/day) was observed initially following injury. This was followed by induction of metabolism as reflected by a Vmaxinduced of 20.79 +/- 13.71 mg/kg/day, which was approximately twofold higher than reported values for nonstressed children. Children with severe, acute neurotrauma were found to have markedly altered protein binding and phenytoin metabolism. |
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Authors:
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C D Stowe; K R Lee; S A Storgion; S J Phelps |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of clinical pharmacology Volume: 40 ISSN: 0091-2700 ISO Abbreviation: J Clin Pharmacol Publication Date: 2000 Dec |
Date Detail:
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Created Date: 2000-12-11 Completed Date: 2000-12-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0366372 Medline TA: J Clin Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 1452-61 Citation Subset: IM |
Affiliation:
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University of Arkansas for Medical Sciences, Little Rock, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anticonvulsants
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blood,
pharmacokinetics* Brain Injuries / metabolism* Child Child, Preschool Female Humans Male Oxidation-Reduction / drug effects Phenytoin / blood, pharmacokinetics* Protein Binding / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 57-41-0/Phenytoin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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