Chronic treatment of rats with primidone causes depletion of pteroylpentaglutamates in liver.
Anticonvulsants have been shown to cause folacin deficiency in chronically treated epileptic patients. However, a mechanism for this depletion has not been established. In the present study, the effects of chronic primidone treatment on folates in the rat were investigated. Using a continuously protective relatively nontoxic regimen of oral administration, it was found that primidone (100 mg/kg, twice per day) caused a decrease of pteroylpentaglutamates in the liver to less than half the control value within 1 wk. Total liver folacin concentration decreased by 30% in the first week followed by a slow gradual further decline with continuing treatment. Plasma folacin exhibited essentially the same pattern but no effect was observed on brain folacin concentration. Primidone was not detectable in plasma 12 h after gavage but phenobarbital was detectable. These data are consistent with the hypothesis that the anticonvulsant primidone (and/or phenobarbital) cause folate depletion via interaction with folate metabolism.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005492:Folic Acid / Q000031:analogs & derivatives*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011324:Primidone / Q000494:pharmacology*; D011624:Pteroylpolyglutamic Acids / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011624:Pteroylpolyglutamic Acids; D011324:Primidone; D005492:Folic Acid