The Pharmacokinetics of Fumaric Acid Esters Reveal Their In Vivo Effects

Abstract

Fumaric acid ester-based drugs are used for the treatment of psoriasis and multiple sclerosis. All licensed fumaric acid ester drugs contain dimethylfumarate (DMF) as the main active component. Due to the expanding use of oral DMF there is growing scientific interest in determining its as-yet-unknown mechanism of action. However, the pharmacology and chemistry of DMF are often not fully considered in the design and interpretation of experiments; namely, that while DMF is plasma-membrane permeable and has strong effects on many cell types in vitro, it is rapidly metabolized into membrane-impermeable monomethylfumarate (MMF) in vivo. This can lead to significant biological effects being erroneously assigned to DMF. Understanding the pharmacology of DMF means that future work can more closely reflect the state in vivo.