Methotrexate ra folic acid category for the anticancer agent is a cell cycle specific drugs.Methotrexate ra experimental study in 1949 by the Seager synthesis, for the treatment of leukemia in 1953, and achieved a certain effect. MTX and folic acid chemical structure similar to a major role in cell cycle S phase, in vivo competitive with dihydrofolate reductase (DHFR) combined to stop the dihydrofolate reductase hydrogen as prisoners of folic acid, leading to cast a slight ridge and nucleotide eyelashes required for synthesis of reduced folate deficiencies. A high degree of affinity with the DHFR MTX at high concentrations (> 10mol / L), slightly inhibited thymus nuclear Xi Wan synthase, blocking the nuclear tone deoxy hospital of urine slightly acid (dUMP) into the nuclear tone deoxy chest slightly Court (dTMP ), directly affect DNA synthesis. As FH4 (leucovorin) as the number of coenzyme involved in some of the amino acid metabolism, therefore, MTX also affects the role of the amino acid metabolism, protein synthesis obstacles.
MTX orally easy to absorb, but large doses (> 30mg/ml) absorption is incomplete. Methotrexate ra experimental study plasma concentrations when injected directly dose related. 50% of drug into the blood and plasma protein binding, one through the blood brain barrier easily, blood concentration in CSF concentrations of 5%, but large doses through the blood – brain barrier. After dark a considerable injection of doses up to the systemic circulation. Curve of plasma MTX disappearance of three-phase, half life O.75h, 3.5h and Z.7h. Drugs in the liver, kidney and intestinal epithelium in high concentration, with high content of these organs on DHFR. Drugs can also be distributed to the chest, abdomen and other body cavity, when there are chest, ascites, MTX can be used as reservoir. Prototype with the urinary excretion of drugs, most of the drug excreted in the former 8h, 48h 40% -90% within the discharge. A small amount of MTX excreted through the biliary tract. A small number in the liver and kidney tissues retained a few weeks to several months. Pleural or peritoneal effusion in a case, the drug significantly delayed the clearance rate, clearance rate of individuals vary widely, even more elderly patients.
The role of MTX can Beijia cool tetrahydrofolate (CF) of the confrontation, commonly used CF as a clinical antidote. The drug is cell cycle specific drugs acting on the S, on the G1 phase / S phase boundary of a delayed effect.
Methotrexate ra experimental study, when the VCR and MTX in combination, first with VCR, MTX can prevent the outflow from the cells, improve the outcome. In addition, after the first use of MTX with 5 FU can increase the cell killing one. After the first use of MTX with L-ASP, MTX toxicity can be reduced.