Document Detail


Pharmacokinetic observations of phenytoin disposition in the newborn and young infant.
MedLine Citation:
PMID:  871217     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pharmacokinetic profile of phenytoin (DPH) was studied in 30 infants aged 2 days to 96 weeks. The plasma DPH half-life during the first week of life in term infants was prolonged and very variable (20-7 +/- 11-6 h, mean +/-SD). Thereafter the plasma half-life was much shorter (7-6 +/- 3-5 h). In preterm infants the half-life was much longer (75-4 +/- 64-5 h) and more variable. The mean apparent volume of distribution was similar in these groups of infants: preterm newborn 0-80 +/- 0-22 l/kg, term infants during the first week of life 0-80 +/- 0-26 l/kg, and term infants greater than 2 weeks of age 0-73 +/- 0-18 l/kg. Predictions of steady-state plasma DPH concentrations, based on these kinetic parameters, were confirmed. Very low "trough" plasma DPH concentrations were observed after the 14th postnatal day in 19 infants receiving 8 mg/kg per 24 h orally. On the other hand, infants of less than one week of age receiving the same dose, especially if preterm, frequently showed drug accumulation to toxic plasma DPH concentrations. The impaired binding of DPH to newborn plasma protein was confirmed but "normal adult values" were approached by the age of 3 months. An intravenous loading dose of 8 mg/kg (sodium phenytoin) can be expected to generate a mean plasma DPH concentration of 10 mg/l (40 micronmol/l) in the newborn. Loading doses of up to 12 mg/kg were given without untoward effects. During the first week or so of life plasma Dph half-life is so variable that no fixed dosage regimen can be derived from the available data. Beyond the second week of life, however, a dose of 8 mg/kg per 24 h is probably inadequate for most infants.
Authors:
P M Loughnan; A Greenwald; W W Purton; J V Aranda; G Watters; A H Neims
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Archives of disease in childhood     Volume:  52     ISSN:  1468-2044     ISO Abbreviation:  Arch. Dis. Child.     Publication Date:  1977 Apr 
Date Detail:
Created Date:  1977-06-30     Completed Date:  1977-06-30     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0372434     Medline TA:  Arch Dis Child     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  302-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Half-Life
Humans
Infant
Infant, Newborn*
Kinetics
Phenytoin / blood,  metabolism*
Protein Binding
Radioimmunoassay
Chemical
Reg. No./Substance:
57-41-0/Phenytoin
Comments/Corrections

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


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