Trimetrexate

An antineoplastic and antimicrobial agent

Trimetrexate
INN
Drug class
Routes of administration
Pregnancy category
Bioavailability
Metabolism
Elimination half-life
Excretion
Legal status
CAS Number
PubChem
DrugBank
ChemSpider
KEGG

Trimetrexate is a chemotherapeutic agent used primarily in the treatment of Pneumocystis pneumonia and certain types of cancer. It is a dihydrofolate reductase inhibitor, which means it interferes with the enzyme responsible for the reduction of dihydrofolate to tetrahydrofolate, a form of folic acid necessary for the synthesis of nucleic acids.

Mechanism of Action

Trimetrexate works by inhibiting the enzyme dihydrofolate reductase (DHFR). This inhibition prevents the conversion of dihydrofolate to tetrahydrofolate, thereby depleting the cellular pools of tetrahydrofolate. As a result, the synthesis of thymidylate and purine nucleotides is disrupted, leading to impaired DNA synthesis and cell death. This mechanism is particularly effective against rapidly dividing cells, such as cancer cells and certain types of pathogenic microorganisms.

Clinical Uses

Trimetrexate is primarily used in the treatment of:

• Pneumocystis pneumonia (PCP) in patients who are intolerant to or have failed standard therapies such as trimethoprim-sulfamethoxazole.
• Certain types of cancer, including colorectal cancer and non-small cell lung cancer.

Administration and Dosage

Trimetrexate is administered intravenously. The dosage and duration of treatment depend on the specific condition being treated, the patient's response to therapy, and the presence of any adverse effects. It is often used in combination with leucovorin to mitigate the toxic effects on normal cells.

Side Effects

Common side effects of trimetrexate include:

• Myelosuppression, leading to neutropenia, thrombocytopenia, and anemia.
• Gastrointestinal disturbances, such as nausea, vomiting, and diarrhea.
• Hepatotoxicity, which may manifest as elevated liver enzymes.

Precautions

Due to its potential for severe myelosuppression, patients receiving trimetrexate should be closely monitored with regular blood tests to assess blood cell counts. The use of leucovorin is essential to protect normal cells from the toxic effects of trimetrexate.

Related pages

• Dihydrofolate reductase
• Pneumocystis pneumonia
• Chemotherapy
• Antifolate