Klevator Tác dụng

Pharmacotherapeutic groups: Other immunosuppressants. ATC code: L04AX03.
Pharmacology: Pharmacodynamics: Methotrexate (4-amino-10-methylfolic acid) is a folic acid antagonist that inhibits the reduction of folic acid leading to decreased cellular proliferation. Methotrexate enters the cell through an active transport mechanism of reduced folates.
As a result of the polyglutamylation of methotrexate caused by the folylpolyglutamate synthetase enzyme, the duration of the cytotoxic effect of the drug substance in the cell increases. Methotrexate is a phase-specific substance the main action of which is directed to the S-phase of cell mitosis. It acts generally most effectively on actively proliferating tissues, such as malignant cells, bone marrow, fetal cells, skin epithelium, oral and intestinal mucosa as well as urinary bladder cells. As the proliferation of malignant cells is faster than that of most normal cells, methotrexate can slow down the proliferation of malignant cells without causing irreversible damage to normal tissue.
Calcium folate is a folinic acid that is used to protect normal cells from the toxic effects of methotrexate. Calcium folate enters the cell through a specific transport mechanism, is converted in the cell into active folates, and reverses the inhibition of the synthesis of precursors of DNA and RNA.
Pharmacokinetics: Absorption: The effect of orally administered methotrexate is dependent on the size of the dose. Peak concentrations in serum are reached within 1-2 hours. Generally, a dose of methotrexate of 30 mg/m² or less is absorbed rapidly and completely. The bioavailability of orally administered methotrexate is high (80-100%) at doses of 30 mg/m² or less. At doses above 30 mg/m² absorption becomes nonlinear and absorption at doses exceeding 80 mg/m² is incomplete.
Distribution: Approximately 50% of methotrexate is bound to serum proteins. Upon being distributed into body tissues, high concentrations in the form of polyglutamate are found in the liver, kidneys, and spleen in particular, which can be retained for weeks or months. When administered in small doses, methotrexate passes into the liquor in minimal amounts.
Metabolism: Approx. 10% of the administered methotrexate dose is metabolized in the liver. The principle metabolite is 7-hydroxymethotrexate.
Elimination: Excretion takes place, mainly in unchanged form, primarily via glomerular filtration and active secretion in the proximal tubule.
Approx. 5-20% methotrexate and 1-5% 7-hydroxy methotrexate are eliminated biliary with pronounced enterohepatic circulation.
The terminal half-life is on average 6-7 hours and demonstrates considerable variation (3-17 hours). The half-life can be prolonged to 4 times the normal length in patients who possess a third distribution space (pleural effusion, ascites).
Special populations: In the case of renal insufficiency, elimination is delayed significantly.