Amifostine

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Amifostine
Amifostine.svg
Systematic (IUPAC) name
2-(3-aminopropylamino)ethylsulfanyl
phosphonic acid
Clinical data
AHFS/Drugs.com monograph
Pregnancy cat. C (US)
Legal status -only (US)
Routes Intravenous
Pharmacokinetic data
Bioavailability complete
Half-life 8 minutes
Identifiers
CAS number 20537-88-6 YesY
ATC code V03AF05
PubChem CID 2141
DrugBank DB01143
ChemSpider 2056 YesY
UNII M487QF2F4V YesY
KEGG C06819 YesY
ChEBI CHEBI:2636 YesY
ChEMBL CHEMBL1006 YesY
Chemical data
Formula C5H15N2O3PS 
Mol. mass 214.224 g/mol
 YesY (what is this?)  (verify)

Amifostine is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed by MedImmune under the trade name Ethyol.

Indications[edit]

Amifostine is used therapeutically to reduce the incidence of neutropenia-related fever and infection induced by DNA-binding chemotherapeutic agents including alkylating agents (e.g. cyclophosphamide) and platinum-containing agents (e.g. cisplatin). It is also used to decrease the cumulative nephrotoxicity associated with platinum-containing agents. Amifostine is also indicated to reduce the incidence of xerostomia in patients undergoing radiotherapy for head and neck cancer.

Amifostine was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer. However, while nephroprotection was observed, the probability that amifostine could protect tumors could not be excluded. Additional data have shown that amifostine-mediated tumor protection, in any clincal scenario, is unlikely.

Pharmacokinetics[edit]

WR-1065, 2-((aminopropyl)amino)ethanethiol, the active metabolite of amifostine

Amifostine is an organic thiophosphate prodrug which is hydrolysed in vivo by alkaline phosphatase to the active cytoprotective thiol metabolite, WR-1065. The selective protection of non-malignant tissues is believed to be due to higher alkaline phosphatase activity, higher pH, and vascular permeation of normal tissues.

Amifostine can be administered intravenously or subcutaneously after reconstitution with normal saline. Infusions lasting less than 15 minutes decrease the risk of adverse effects. The patient should be well-hydrated prior to administration.

Mechanism of action[edit]

Inside cells, amifostine detoxifies reactive metabolites of platinum and alkylating agents, as well as scavenges free radicals.[1][2] Other possible effects include accelerated DNA repair,[1] induction of cellular hypoxia,[1] inhibition of apoptosis,[2] alteration of gene expression[2] and modification of enzyme activity.[2]

Adverse effects[edit]

Common side effects of amifostine include hypocalcemia, diarrhea, nausea, vomiting, sneezing, somnolence, and hiccoughs. Serious side effects include: hypotension (found in 62% of patients), erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis, immune hypersensitivity syndrome, erythroderma, anaphylaxis, and loss of consciousness (rare).

Contraindications[edit]

Contraindications to receiving amifostine include hypersensitivity to amifostine and aminothiol compounds like WR-1065. Ethyol contains mannitol.

References[edit]

  1. ^ a b c Kouvaris JR, Kouloulias VE, Vlahos LJ (June 2007). "Amifostine: the first selective-target and broad-spectrum radioprotector". Oncologist 12 (6): 738–47. doi:10.1634/theoncologist.12-6-738. PMID 17602063. 
  2. ^ a b c d "Amifostine : BC Cancer Agency". British Columbia Cancer Agency. 2006-03-01. Retrieved 2011-01-01.