Methotrexate interferes with processes of cell division and inflammation. Due to its structural similarity, methotrexate binds with higher affinity to enzymes for folic acid and blocks them. This inhibits the new synthesis of DNA in the cells and thus cell division. This has a particular effect on tumor cells that are dividing rapidly. Methotrexate is used against rheumatoid arthritis in much lower doses than for tumour treatment. Methotrexate causes ATP to accumulate in the intercellular spaces and suppresses inflammation.
Methotrexate has a bioavailability between 60-90%. The highest plasma concentration is reached after about 2 hours and the average plasma protein binding is about 50%. Methotrexate is metabolized in small amounts in the liver. Over 80% of the dose is excreted unchanged in the urine. The elimination half-life is 5-6 hours at low doses. Higher doses in tumor treatment change this time to approximately 8-15 hours.
Probenecid may slow the elimination of methotrexate, rapidly reaching toxic plasma levels. Colestyramine may have the opposite effect, decreasing efficacy. Interactions may also occur with NSAIDs (non-steroidal anti-inflammatory drugs).