Possible Interaction: Methotrexate and Levomefolate

“ MTX , following by mTHF after a delay of 8-24 h, caused a substantial killing of lymphoid leukemia cells, greater than the effect of either drug alone.”

“Likewise, methyltetrahydrofolate , as a percent of total folate, was reduced 51% in methotrexate-treated rats.”

“ Methotrexate treatment decreased hepatic tetrahydrofolate, methyltetrahydrofolate , and formyltetrahydrofolate, concentrations by 63, 83, and 58%, respectively.”

“These tracer kinetic experiments quantitatively demonstrate the extent to which methotrexate alters the actual carbon flow through the hepatic folate-dependent one-carbon pool, primarily directed at diminishing the reductive carbon flow towards methyltetrahydrofolate and methionine synthesis.”

“Treatment with 800 mg/kg of MTX plus m-THF was 1.5 fold more effective than the same MTX dose plus f-THF in increasing survival time of tumor-bearing mice.”

“The initial uptake and steady-state level of (+)-5-methyltetrahydrofolate were markedly reduced in the resistant sublines as was the case with methotrexate.”

“Folate and methyltetrahydrofolate competitivity inhibited amethopterin uptake with apparent Ki values of 8 and 0.7 muM, respectively.”

“The Ki for amethopterin when added to increasing concentrations of methyltetrahydrofolate was 5.2 muM, a value about the same as that of the Km.”