The pharmacology of methotrexate

Abstract

Ectopic pregnancy (EP) is a major cause of maternal morbidity and mortality. The treatment of this condition is primarily surgical, but medical management in selected cases is safe, effective, cost-effective and eliminates the morbidity of surgery. Methotrexate (MTX) is a folate antagonist that can be used for non-oncologic purposes including the treatment of EP. The dose and duration of MTX therapy for EP is much lower than that used in oncology cases, thus reducing side effects and increasing safety. MTX selectively acts on rapidly dividing cells, such as trophoblast cells which comprise the implantation site of the early gestation. The two most common methods of administering MTX to patients with EP are im. administration of a single-dose, based on body surface area and calculated by the equation 50 mg/m(2) (without the need for leucovorin rescue), or the multiple-dose regimen of 1 mg/kg of MTX, alternating with 0.1 mg/kg of leucovorin rescue. Both methods have a similar side effect profile, resulting in the rare occurrence of nausea, vomiting, stomatitis, elevated liver function tests, anorexia and diarrhoea. The two methods yield success rates similar to those of conservative surgical therapy with similar future fertility. The potential single- and multi-dose methods have never been directly compared, but it appears that the success of multiple dosing is more effective. As the efficacy of MTX therapy is not 100%, women must be followed clinically until there is compete resolution of human Chorionic Gonadotropin (hCG) titres from their serum.

Effects of in vitro exposure of Echinococcus multilocularis metacestodes to cytostatic drugs on in vivo growth and proliferation of the parasite

“…The cytostatic substances applied in this work could have been used in higher concentrations, but higher concentrations of NAV, VCR, or MTX might have exerted toxic effects on laboratory animals. In patients treated with MTX, the life-threatening toxicity is above 1,000 µM (Barnhart et al 2001). MRI appears suitable to monitor in vivo the effects of drug treatments on growth progression or regression of larger Em-metacestode tissues.…”

Methotrexate-mediated inhibition of RAD51 expression and homologous recombination in cancer cells

“…Methotrexate (MTX) is an essential drug in curative chemotherapy regimens and is used to treat patients with certain types of cancer including acute lymphoblastic leukemia, osteosarcoma, and choriocarcinoma. MTX works by disrupting DNA synthesis (Barnhart et al 2001); specifically, MTX inactivates the dihydrofolate reductase (DHFR) enzyme, which leads to the depletion of tetrahydrofolate cofactors that are required for DNA and RNA syntheses (Morales et al 2009). …”

Methotrexate Induces Apoptosis of Postpartum Placental Cytotrophoblasts

“…The main function of MTX is to target the physiological development of cells, especially those which have a high turnover [Barnhart et al, 2001]. Treatment with MTX has been used effectively in early pregnancy [Kurbacher et al, 2002;Mol et al, 2008;Tong et al, 2015].…”