Pemeta-100/Pemeta-500 Mechanism of Action

Pharmacology: Pharmacodynamics: Pemeta-500: Mechanism of action: Pemeta-500 (pemetrexed) is a multi-targeted anti-cancer antifolate agent that exerts its action by disrupting crucial folate-dependent metabolic processes essential for cell replication.
Pharmacodynamic effects: In vitro studies have shown that pemetrexed behaves as a multitargeted antifolate by inhibiting thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), which are key folate-dependent enzymes for the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is rapidly and efficiently converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are even more potent inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumour cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Pharmacokinetics: Pemeta-100/Pemeta-500: Pemetrexed has a plasma elimination half-life of 3.5hours in patients with normal renal function. In vitro data indicate that pemetrexed is about 81% bound to plasma proteins. It undergoes limited hepatic metabolism, and about 70 to 90% of a dose is eliminated unchanged in the urine within 24 hours.