Avoid the christmas cheer if you want DMF cheer. How is active DMF formed


Dimethyl fumarate (DMF) breaks down into the active molecule called monomethyl fumarate a methyl group is .on carbon atom and three hydrogen molcules..the other carbon bond forms part of the backbone of the molecule. In the diagram below it is on the end of the O (oxygen) atom with the single line (bond). Dimethyl (has two) and mono methyl has (one). In this study they look how the active molecule is made and this is by a protein called CES1. This found in the liver (www.biogps.org) and so this is likely to be a place where the dimethyl fumarate is activated. In this paper they show that this break down is inhibited by alcohol=ethanol

However we know that dimethyl fumarate is affected by alcohol because in the Product information it says “consumption of more than a small quantity (more than 50 ml) of strong alcoholic drinks (more than 30% alcohol by volume, e.g. spirits) should be avoided within an hour of taking Tecfidera (trade name of dimethyl fumarate), as alcohol can interact with this medicine. This could cause inflammation of the stomach (gastritis), especially in people already prone to gastritis”.

So drink and drink or avoid drink and dimethyl fumarate

Yang B, Parker RB, Meibohm B, Temrikar ZH, Srivastava A, Laizure SC. Alcohol inhibits the metabolism of dimethyl fumarate to the active metabolite responsible for decreasing relapse frequency in the treatment of multiple sclerosis. PLoS One. 2022 Nov 28;17(11):e0278111

Dimethyl fumarate (DMF) is a first-line prodrug (broken down to the active drug) for the treatment of relapsing-remitting multiple sclerosis (RRMS) that is completely metabolized to monomethyl fumarate (MMF), the active metabolite, before reaching the circulation (blood). Its metabolism has been proposed to be due to ubiquitous (present everywhere) esterases (enzymes acting on chemical [ester] bonds) in the intestines and other tissues, but the specific enzymes involved are unknown. We hypothesized based on its structure and extensive presystemic metabolism that DMF would be a carboxylesterase substrate subject to interaction with alcohol. We sought to determine the enzymes(s) responsible for the extensive presystemic metabolism of DMF to MMF and the effect of alcohol on its disposition by conducting metabolic incubation studies in human recombinant carboxylesterase-1 (CES1), carboxylesterase-2 (CES2) and human intestinal microsomes (HIM) [part of cell cytoplasm that had degrading enzymes], and by performing a follow-up study in an mouse model. The in vitro (in a test tube) incubation studies demonstrated that DMF was only metabolized to MMF by CES1. Consistent with the incubation studies, the mouse pharmacokinetic study demonstrated that alcohol decreased the maximum concentration of MMF in the plasma (blood) and the brain after dosing with DMF. We conclude that alcohol may markedly decrease exposure to the active MMF metabolite in the plasma and brain potentially decreasing the effectiveness of DMF in the treatment of RRMS.

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