Absorption, Distribution and Excretion
Similar to its bioequivalent counterpart, dimethyl fumarate, dimethyl fumarate is rapidly absorbed from the gastrointestinal tract after administration. Following oral administration of dimethyl fumarate (MMF), the median time to peak concentration (Tmax) is 2.5–3 hours, and the mean plasma concentration (Cmax) is 2.11 mg/L. Similar mean Tmax and Cmax were observed in healthy volunteers after administration of the bioequivalent dimethyl fumarate. In patients with multiple sclerosis (MS), the mean steady-state concentration after twice-daily administration of this metabolite is estimated to be 8.32 mg·hr/L. The mean AUC0–∞ of the active metabolite is 88 mg × min L−1. Food intake appears to significantly reduce the Cmax of the active metabolite MMF compared to a fasting state. Dimethyl fumarate is exhaled as carbon dioxide. The amount of drug detected in urine is extremely small, less than 0.3% of the ingested dose. The inactive metabolite 2-hydroxyethylsuccinimide (HES), accounting for 58-63% of the ingested dose, is also excreted in urine. The apparent volume of distribution is 72 to 83 liters. The active metabolite of dimethyl fumarate, monomethyl fumarate (MMF), can cross the blood-brain barrier. The FDA does not provide clearance information for dimethyl fumarate on its label, but clinical studies of its active metabolite, monomethyl fumarate, showed an average total apparent plasma clearance of 1.54 mg/L after oral administration. Metabolites/Metabolites Dimethyl fumarate and its bioequivalent, dimethyl fumarate, are primarily metabolized in the liver by esterases. These enzymes are abundant in the gastrointestinal tract, tissues, and blood. The drug is metabolized by esterases to produce the active metabolite, monomethyl fumarate (MMF), which then enters systemic circulation. In addition, the main inactive metabolite 2-hydroxyethylsuccinimide (HES) is produced, along with small amounts of methanol and another inactive metabolite, RDC-8439. Following esterase metabolism, the tricarboxylic acid cycle (TCA cycle) further metabolizes MMF. The main metabolites of MMF in plasma include fumarate, citric acid, and glucose. Methanol is the main metabolite of dimethyl fumarate, but a minor metabolite, which reduces the risk of gastrointestinal side effects.

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Biological Half-Life
The terminal half-life of monomethyl fumarate (MMF), the active metabolite of dimethyl fumarate, is estimated to be 1 hour.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Currently, there is no information regarding the clinical use of dimethyl fumarate during lactation. However, the active metabolite of dimethyl fumarate, monomethyl fumarate, appears to be present in low levels in breast milk and is not expected to have any adverse effects on breastfed infants. Based on clinical data from over 20 infants who were exposed to dimethyl fumarate through breast milk, its use during lactation is acceptable, at least after the infant is one month old. Weight gain and developmental milestones in breastfed infants should be monitored, especially for younger, exclusively breastfed infants. Some authors also recommend monitoring for flushing, vomiting, and diarrhea in breastfed infants.
◉ Effects on Breastfed Infants
Between 2015 and 2020, 26 women taking dimethyl fumarate for relapsing-remitting multiple sclerosis were followed up during 29 pregnancies. Dimethyl fumarate was administered until the 24th week of gestation and resumed one month postpartum. 22 of the 26 mothers breastfed (duration not specified) for 4 to 7 months. Infants were monitored for up to 3 years for infections and developmental delays. All children were at the 70th and 95th percentiles for their age. The authors concluded that continued use of dimethyl fumarate during breastfeeding is safe even if infants were not exposed to it in the first month after birth.
◉ Effects on lactation and breast milk
No published information found as of the revision date.
Protein binding
The plasma protein binding of the active metabolite MMF of dimethyl fumarate ranges from 27% to 45%.

:https://multiplesclerosisnewstoday.com/2019/02/27/fda-review-nda-diroximel-fumarate-relapsing-forms-ms/

Multiple sclerosis (MS) is a chronic, disabling neurological disorder that causes severe cognitive and physical symptoms, significantly impacting patients' quality of life. It is a leading cause of non-traumatic neurological dysfunction in young adults in North America and Europe. Relapsing-remitting MS is characterized by periodic remissions and relapses of neurological symptoms. More than 80% of MS patients have relapsing-remitting MS. Dimethyl fumarate is a novel fumarate ester used to treat various types of relapsing-remitting MS. It is bioequivalent to dimethyl fumarate (originally manufactured in 2013) but has a lower likelihood of causing gastrointestinal side effects due to its unique chemical structure. Dimethyl fumarate was developed by Alkermes in collaboration with Biogen and received FDA approval in October 2019 and EMA approval in November 2021.
See also: Monomethyl fumarate (containing the active ingredient). Drug Indications Dimethyl fumarate is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (MS), particularly active secondary progressive MS and clinically isolated syndrome, as well as relapsing-remitting MS. Dimethyl fumarate is indicated for the treatment of adult patients with relapsing-remitting MS (see Section 5.1 for important information on populations with proven efficacy). Mechanism of Action The mechanism of action of this drug in MS is not fully understood. Dimethyl fumarate is thought to modulate cellular signaling pathways, thereby producing beneficial immunoprotective and neuroprotective effects. Monomethyl fumarate (MMF) is the active metabolite of dimethyl fumarate and activates the nuclear factor (erythrocyte-derived 2)-like 2 (Nrf2) pathway in the human body. This pathway is the cellular response to oxidative stress. Furthermore, MMF is a nicotinic acid receptor agonist under laboratory conditions. The relevance of this finding to the treatment of multiple sclerosis (MS) is currently unclear. The mechanism by which this drug has fewer gastrointestinal side effects is believed to be due to the absence of a methanol leaving group in its chemical structure, which is replaced by an inert 2-hydroxyethylsuccinimide.

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Pharmacodynamics
Dimethyl fumarate can relieve neurological symptoms of relapsing MS, and has fewer gastrointestinal side effects than its bioequivalent, dimethyl fumarate. It is important to note that dimethyl fumarate can cause angioedema, allergic reactions, hepatotoxicity, flushing, lymphopenia, and progressive multifocal leukoencephalopathy (PML). If PML is suspected, or if an allergic reaction or angioedema occurs, dimethyl fumarate should be discontinued immediately. Liver function and total bilirubin levels should be monitored before starting dimethyl fumarate and during treatment. Complete blood counts (CBCs) should be performed before starting dimethyl fumarate, 6 months after starting treatment, and every 6 to 12 months thereafter. Treatment should be discontinued if the lymphocyte count is below 0.5 × 10⁹/L and persists for more than 6 months.

C11H13NO6

255.224023580551

255.074

1577222-14-0

73330464

White to off-white solid powder

1.3±0.1 g/cm3

441.0±25.0 °C at 760 mmHg

102-106

220.5±23.2 °C

0.0±1.1 mmHg at 25°C

1.515

-0.24

0

6

7

18

384

0

COC(=O)/C=C/C(=O)OCCN1C(=O)CCC1=O

YIMYDTCOUQIDMT-SNAWJCMRSA-N

InChI=1S/C11H13NO6/c1-17-10(15)4-5-11(16)18-7-6-12-8(13)2-3-9(12)14/h4-5H,2-3,6-7H2,1H3/b5-4+

2-(2,5-dioxopyrrolidin-1-yl)ethyl methyl fumarate

ALKS-8700; BIIB-098; VUMERITY™; ALKS8700; ALKS 8700; ALKS-8700

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~489.77 mM)
H2O : ≥ 10 mg/mL (~39.18 mM)

Solubility in Formulation 1: 2.08 mg/mL (8.15 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (8.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (8.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)