Document Detail

Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin.
MedLine Citation:
PMID:  1547769     Owner:  NLM     Status:  MEDLINE    
Chronic phenytoin (PHT) treatment has long been associated with folate deficiency. It has been suggested that pH changes in the gut associated with PHT ingestion may be responsible for decreased folate uptake either by direct inhibition of folate transport into the intestinal mucosa or by inhibition of folate conjugase activity. To examine these possibilities, rats were gavaged chronically with PHT using either the sodium salt (NaPHT) or the free acid (HPHT) in the presence of folic acid as the dietary source of folate. The NaPHT caused a greater depletion of folate in the liver and brain and a significant increase in methylenetetrahydrofolate reductase activity in the liver. The HPHT caused a significantly decreased weight gain over the 8 weeks of treatment and resulted in a much higher liver PHT concentration and a slightly lower plasma PHT concentration. These data support the hypothesis that PHT-induced changes in pH in the gut affect the enterohepatic circulation of folate.
G F Carl; M L Smith
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Epilepsia     Volume:  33     ISSN:  0013-9580     ISO Abbreviation:  Epilepsia     Publication Date:    1992 Mar-Apr
Date Detail:
Created Date:  1992-04-20     Completed Date:  1992-04-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  372-5     Citation Subset:  IM    
Medical Research, VA Medical Center, Augusta, Georgia 30910.
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MeSH Terms
Brain Chemistry / drug effects
Disease Models, Animal
Enterohepatic Circulation / drug effects
Folic Acid / analysis,  metabolism*,  pharmacokinetics
Folic Acid Deficiency / chemically induced
Gastric Acid / metabolism
Hydrogen-Ion Concentration / drug effects
Liver / chemistry,  drug effects
Phenytoin / adverse effects,  pharmacology*
Rats, Inbred Strains
Weight Gain / drug effects
Reg. No./Substance:
57-41-0/Phenytoin; 59-30-3/Folic Acid

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

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