Methotrexate, an antimetabolite, is clinically useful in:

Methotrexate route(s) of administration:

Primary mechanism of action associated with methotrexate activity, especially at high doses associated with cancer chemotherapeutic activity: inhibition of dihydrofolate reductase.

The high-dose, anti-proliferative actions of methotrexate, the basis of its activity in cancer chemotherapy, may not be central at low doses used in methotrexate treatment of inflammatory bowel disease. Potential methotrexate mechanism(s) of action that may be important for its efficacy in IBD include(s):

Methotrexate may induce "programmed cell death" a.k.a. apoptosis, resulting in death of activated T-cell lymphocytes.

Methotrexate appears effective both in induction and maintenance of remission in patients with Crohn's disease and ulcerative colitis.

At higher doses, adverse effects of methotrexate include:

Typical, severe adverse effects at high dose methotrexate are uncommon at doses used in treatment of inflammatory bowel disease. However, residual risk can be reduced by folate supplementation.

Methotrexate is typically administered by the parenteral route of administration because of unpredictable intestinal absorption in the presence of intestinal disease. The parenteral route administration is preferable even at higher dose methotrexate because of unpredictable intestinal absorption characteristics.

Methotrexate may be used in combination with anti-TNF-α antibody therapeutics.

For treatment of Crohn's disease, methotrexate is usually administered subcutaneously or intramuscularly.

Active tubular secretion is likely responsible for 90% of administered methotrexate appearing unchanged in the urine.

Drugs that inhibit renal excretion of methotrexate may cause methotrexate-related toxicity. which one(s) of the following may interfere with methotrexate renal excretion?