Document Detail


Altered phenytoin pharmacokinetics in children with severe, acute traumatic brain injury.
MedLine Citation:
PMID:  11185666     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
C D Stowe; K R Lee; S A Storgion; S J Phelps
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  40     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2000-12-11     Completed Date:  2000-12-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1452-61     Citation Subset:  IM    
Affiliation:
University of Arkansas for Medical Sciences, Little Rock, USA.
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MeSH Terms
Descriptor/Qualifier:
Anticonvulsants / 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:
0/Anticonvulsants; 57-41-0/Phenytoin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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