MET Fumarate

Overview

MET Fumarate, or Methotrexate Fumarate, is a pharmaceutical compound predominantly used in the treatment of autoimmune diseases and certain types of cancer. It is a folate analog that functions as a disease-modifying anti-rheumatic drug (DMARD) and an antimetabolite, disrupting DNA synthesis in rapidly proliferating cells. This mechanism of action makes it an essential medication for conditions such as rheumatoid arthritis, psoriasis, and specific malignancies like leukemia.

Chemical Composition and Structure

MET Fumarate combines methotrexate, a dihydrofolate reductase (DHFR) inhibitor, with fumarate, an organic compound playing key roles in metabolic pathways. The molecular formula for MET Fumarate is C20H22N8O5•C4H4O4, reflecting its complex structure. Its white crystalline appearance, stability under standard storage conditions, and solubility in water and saline solutions make it suitable for a variety of pharmaceutical formulations, including oral tablets, injections, and topical treatments.

Mechanism of Action

The primary mechanism of MET Fumarate involves inhibition of the DHFR enzyme, which is critical for the production of tetrahydrofolate (THF). THF is a necessary co-factor in the synthesis of purines and thymidylate, essential precursors for DNA and RNA production. By blocking DHFR, MET Fumarate reduces the reproductive capabilities of rapidly dividing cells. This feature is particularly effective in controlling hyperactive immune cell activity in autoimmune conditions and slowing cancer cell growth in malignancies. Fumarate plays an auxiliary role, enhancing the compound’s bioavailability and stabilizing methotrexate’s activity.

Pharmacological Applications

1. Rheumatoid Arthritis

MET Fumarate is widely prescribed as a first-line treatment for rheumatoid arthritis (RA). By modulating the immune response, it minimizes joint inflammation, slows disease progression, and reduces long-term joint damage. Its weekly dosing regimen, combined with its ability to be used alongside folic acid supplementation, improves tolerability and patient compliance.

2. Psoriasis and Psoriatic Arthritis

The drug is effective in managing moderate to severe chronic plaque psoriasis and psoriatic arthritis by suppressing the immune system’s overactive response, leading to a reduction in skin lesions and inflammation.

3. Cancer Treatment

MET Fumarate is employed in higher doses for chemotherapy regimens targeting acute lymphoblastic leukemia (ALL), choriocarcinoma, and certain solid tumors. Its cytotoxic properties specifically target malignant cells while sparing normal, slower-dividing tissues to the greatest extent possible.

Pharmacokinetics

MET Fumarate exhibits predictable pharmacokinetics, with absorption rates varying by the chosen route of administration. Oral bioavailability can range between 40-90%, depending on dose size. Peak plasma levels are typically reached within 1-4 hours after ingestion. The compound is metabolized hepatically, primarily through aldehyde oxidase, and excreted primarily via the renal pathway. Its half-life averages 3-10 hours, making it suitable for weekly dosing in most cases, although therapeutic adjustments are necessary for patients with impaired renal function.

Formulations and Dosing

MET Fumarate is available in various forms to optimize its use across medical disciplines:

• Oral Tablets: Widely used for RA and psoriasis treatment, available in 2.5 mg, 5 mg, and 10 mg strengths. Typical doses range from 7.5 mg to 25 mg per week.
• Injectable Solutions: Primarily used in oncology, allowing for high-dose administration with a rapid onset of action. Concentrations range from 25 mg/mL