trimetrexate

Trimetrexate is a medication that belongs to a class of drugs known as antifolates. Its chemical structure is similar to folic acid, a vitamin essential for cell growth and function. Trimetrexate works by inhibiting an enzyme called dihydrofolate reductase (DHFR). This enzyme is crucial for the metabolism of folic acid, and by blocking its activity, trimetrexate prevents cells from producing the necessary components for DNA and RNA synthesis. This disruption in DNA and RNA production ultimately halts cell division and growth.

Historically, trimetrexate has been used in the treatment of certain types of cancer, particularly as an alternative agent for patients with advanced colorectal cancer who have not responded to other therapies. It has also been investigated for its use in treating Pneumocystis jirovecii pneumonia (PJP), a serious lung infection that can occur in individuals with weakened immune systems, such as those with HIV/AIDS. Its mechanism of action against PJP is also related to its ability to inhibit DHFR, an enzyme vital for the survival of the Pneumocystis organism.

The administration of trimetrexate is typically done intravenously. Due to its mechanism of action, which affects rapidly dividing cells, trimetrexate can cause side effects. These commonly include myelosuppression, leading to decreased blood cell counts, as well as gastrointestinal issues like nausea and diarrhea. To mitigate some of the toxic effects, especially on healthy bone marrow cells, trimetrexate is often given concurrently with leucovorin rescue. Leucovorin is a form of folic acid that can bypass the DHFR enzyme, thereby protecting healthy cells from the antifolate effects of trimetrexate.