Abstract
Reversal of the effects of antifolates requires effective expansion of the body pool of reduced folate coenzymes. In the past, this has required parenteral use of 5-formyltetrahydrofolate. By use of Radio-labeled 5-formyltetrahydrofolate, we showed that its oral administration also expands the body reduced folate pool. After oral administration of 5-formyl-
14
C-tetrahydrofolate-
3
H to fasting subjects, the labels appeared in the serum, peaking at 60 minutes. Chromatographic analysis showed that the labeled serum folate was principally the naturally occurring 5-methyltetrahydrofolate-
3
H. Close to 90 per cent of orally administered 5-formyltetrahydrofolate appeared to be absorbed. The most constant labeled urinary folate was found to be 10-formyltetrahydrofolate or 5, 10-methenyltetrahydrofolate. Renal excretion of labeled 5-formyltetrahydrofolate occurred at undetectable serum levels whereas renal excretion of labeled 5-methyltetrahydrofolate was proportional to its serum concentration.
OF the reduced folates, the one that is chemically most stable
1
,
2
and is therefore used therapeutically to reverse
3
,
4
the effects of folate antagonists, such as methotrexate, is 5-formyltetrahydrofolate (leucovorin, citrovorum factor, 5-formylFH
4
). However, in vitro, under acid conditions such as exist in the stomach, 5-formylFH
4
isomerizes to the stable 5, 10-methenylFH
4
, which, under neutral pH conditions such as exist in the jejunum, isomerizes in turn to the readily oxidized and unstable 10-formylFH
4
.
1
Therefore, in the past, 5-formylFH
4
has always been administered parenterally, and, indeed, its oral absorption has only recently been the . . .