Pemetrexed

drugbox
IUPAC_name = 2- [4- [2-(4-amino-2-oxo-3,5,7-triazabicyclo [4.3.0] nona-3,8,10-trien-9-yl)ethyl] benzoyl] aminopentanedioic acid


CAS_number = 137281-23-3
ATC_prefix = L01
ATC_suffix = BA04
ATC_supplemental =
PubChem = 60843
DrugBank = APRD00573
C = 20 | H = 21 | N = 5 | O = 6
molecular_weight = 427.411 g/mol
bioavailability = NA
protein_bound = 81%
metabolism = Negligible
elimination_half-life = 3.5 hours
excretion = Renal
licence_EU = Alimta
licence_US = Pemetrexed
pregnancy_US = D
legal_UK = POM
legal_US = Rx-only
routes_of_administration = IV

Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma as well as non-small cell lung cancer.

History

The molecular structure of pemetrexed was developed by Edward C. Taylor at Princeton University and clinically developed by Indianapolis based drug maker, Eli Lilly and Company in 2004.

Mechanism of action

Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis—thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyl transferase (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.

Clinical use

In February 2004, the Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of the lining of the lung, in combination with cisplatin. In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against of locally-advanced and metastatic non-small cell lung cancer, or NSCLC, in patients with non-squamous histology. Trials are currently testing it against esophagus and other cancers.

Patients are required to be on folic acid and vitamin B12 supplementation when they are on pemetrexed therapy. (In clinical trials for mesothelioma, folic acid and B12 supplementation reduced the frequency of adverse events.) It is also recommended for patients to be on a steroid (e.g. dexamethasone 4mg twice daily) on the day prior, day of, and day after pemetrexed infusion to avoid skin rashes.

External links

* [http://www.alimta.com Alimta website]
* [http://www.virtualcancercentre.com/drugs.asp?drugid=3052 Alimta / Pemetrexed] Virtual Cancer Centre
* [http://www.cancer.gov/cancertopics/druginfo/pemetrexeddisodium NCI Drug Information Summary on Pemetrexed Disodium]