| Effects of salicylate on maternal and fetal phenytoin pharmacokinetics in rats. | |
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MedLine Citation:
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PMID: 6145554 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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P A Cleveland; C T Ueda |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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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:
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Created Date: 1984-08-01 Completed Date: 1984-08-01 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 285-90 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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