Document Detail


Effects of salicylate on maternal and fetal phenytoin pharmacokinetics in rats.
MedLine Citation:
PMID:  6145554     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of salicylate on maternal and fetal phenytoin pharmacokinetics were investigated in 19-day pregnant Sprague-Dawley rats after a 5 mg/kg bolus injection of 14C-phenytoin was given with and without (control) prior salicylate (75 mg/kg) treatment. Maternal plasma and fetal whole body samples were obtained at various times after the phenytoin bolus and evaluated simultaneously using a three-compartment maternal-fetal model. An increase in maternal plasma phenytoin clearance, central compartment volume, and over-all apparent volume of distribution with no change in the terminal first order hybrid disposition rate constant (beta) was observed in the salicylate-treated rats. These dispositional changes were consistent with the elevations in serum free or unbound phenytoin concentrations observed in vitro in the presence of salicylate. The maternal-to-fetal clearance of phenytoin was faster in the rats given sodium salicylate. However, the maternal-to-fetal (k13) as well as fetal-to-maternal (k31) phenytoin transfer rate constants were not altered by the salicylate treatment. Additionally, no changes in the apparent fetal phenytoin volume of distribution or area under the fetal phenytoin concentration-time curves were seen. Although the maternal pharmacokinetics of phenytoin were altered by sodium salicylate co-administration, the extent of fetal exposure to phenytoin did not change.
Authors:
P A Cleveland; C T Ueda
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  12     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1984 May-Jun
Date Detail:
Created Date:  1984-08-01     Completed Date:  1984-08-01     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  285-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Proteins / metabolism
Female
Fetus / metabolism
Kinetics
Maternal-Fetal Exchange / drug effects*
Models, Biological
Phenytoin / metabolism*
Pregnancy
Protein Binding
Rats
Rats, Inbred Strains
Salicylic Acid
Salicylic Acids / pharmacology*
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/Salicylic Acids; 57-41-0/Phenytoin; 69-72-7/Salicylic Acid

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


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