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Phenytoin‐Folate Interactions: Differing Effects of the Sodium Salt and the Free Acid of Phenytoin
Author(s) -
Carl G. F.,
Smith M. L.
Publication year - 1992
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1992.tb02330.x
Subject(s) - phenytoin , chemistry , medicine , folic acid , endocrinology , ingestion , enterohepatic circulation , sodium , bioavailability , pharmacology , metabolism , biochemistry , epilepsy , biology , organic chemistry , neuroscience
Summary: 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 folk 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.