Overview
| Generic Names: | TMQ; TMX; Trimetrexato [INN-Spanish]; Trimetrexatum [INN-Latin] |
|---|---|
| Trade Names: | Neutrexin |
| PharmGKB Accession Id: | PA451790 |
Description
A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. PubChem (source: Drug Bank)
Indication
For use, with concurrent leucovorin administration (leucovorin protection), as an alternative therapy for the treatment of moderate-to-severe <i>Pneumocystis carinii</i> pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Also used to treat several types of cancer including colon cancer. (source: Drug Bank)
ATC Therapeutic Category
- P01AX:Other agents against amoebiasis and other protozoal diseases
Pharmacology, Interactions, and Contraindications
Mechanism Of Action
In vitro studies have shown that trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of p.r.n. biosynthesis. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death. (source: Drug Bank)
Pharmacology
Trimetrexate, a non-classical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase (DHFR). During DNA synthesis and cellular reproduction, folic acid is reduced to tetrahydrofolic acid by the enzyme folic acid reductase. By interfering with the reduction of folic acid, trimetrexate interferes with tissue cell reproduction. Generally, the most sensitive cells to the antimetabolite effect of trimetrexate are those cells which are most actively proliferating such as malignant cells, dermal epithelium, buccal and intestinal mucosa, bone marrow, fetal cells, and cells of the urinary bladder. Because the proliferation of cells in malignant tissues is greater than in most normal tissues, trimetrexate may impair the growth of the malignant tissues without causing irreversible damage to normal tissues. Due to very serious and potentially life-threatening side-effects of this drug, leucovorin must be co-administered for at least 72 hours after the last dose. (source: Drug Bank)
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
Hepatic. Preclinical data strongly suggest that the major metabolic pathway is oxidative O-demethylation, followed by conjugation to either glucuronide or the sulfate. (source: Drug Bank)
Protein Binding
95% (over the concentration range of 18.75 to 1000 ng/mL) (source: Drug Bank)
Toxicity
The LD<sub>50</sub> of intravenous trimetrexate in mice is 62 mg/kg (186 mg/m<sup>2</sup>). Myelosuppression is a dose-limiting toxic effect. (source: Drug Bank)
Isomeric SMILES Code:
Cc1c(ccc2c1c(nc(n2)N)N)CNc3cc(c(c(c3)OC)OC)OC (source: Drug Bank)
A list of non-curated publications that mention this drug along with other genes is available.
Drug Targets
| Gene | Description | |
|---|---|---|
| DHFR |
|
(source: Drug Bank) |
A list of non-curated publications that mention this drug along with other drugs is available.
Drug Interactions
| Drug | Description | |
|---|---|---|
| acenocoumarol |
|
The anticoagulant effect of Acenocoumarol, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate. Monitor for changes in the anticoagulant effects of warfarin and other coumarin derivatives during concomitant use. (source: Drug Bank) |
| digoxin |
|
The absorption of Digoxin, a cardiac glycoside, may be decreased by antineoplastic agents such as Trimetrexate. Liquid forms of Digoxin do not appear to be significantly affected. Monitor Digoxin tablet efficacy if Trimetrexate therapy is initiated, discontinued or if the dose is altered. (source: Drug Bank) |
| warfarin |
|
The anticoagulant effect of Warfarin, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate. Monitor for changes in the anticoagulant effects of warfarin and other coumarin derivatives during concomitant use. (source: Drug Bank) |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
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LinkOuts
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Non-Curated Publications
A list of non-curated publications that mention this drug is available.