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Serum disappearance curves in dogs after the intravenous injection of radioactive methotrexate, 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and folic acid followed first-order kinetics with half-disappearance times ranging from 1.3 to 9 hr respectively. Equilibration of spinal fluid tritium levels with those in serum was rapid (3.0 hr) for both of the reduced folates but was not observed at any time after folic acid and methotrexate. The only radioactive folate identified in the spinal fluid after intravenous injection of either 5-formyltetrahydrofolate or folic acid, as well as 5-methyltetrahydrofolate was 5-methyltetrahydrofolate. These findings indicated that 5-methyltetrahydrofolate was taken up preferentially into the spinal fluid and that the other folate congeners were converted to this compound before uptake. Diphenylhydantoin administration did not alter the uptake of 5-methyltetrahydrofolate into the spinal fluid but was associated with reduced renal excretion of this compound.

Transport characteristics of folates in cerebrospinal fluid; a study utilizing doubly labeled 5-methyltetrahydrofolate and 5-formyltetrahydrofolate