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 Amifostine

Amifostine trihydrate  is the trihydrate form of a phosphorylated aminosulfhydryl compound. After dephosphorylation of amifostine by alkaline phosphatase to an active free sulfhydryl (thiol) metabolite, the thiol metabolite binds to and detoxifies cytotoxic platinum-containing metabolites of cisplatin and scavenges free radicals induced by cisplatin and ionizing radiation. The elevated activity of this agent in normal tissues results from both the relative abundance of alkaline phosphatase in normal tissues and the greater vascularity of normal tissues compared to tumor tissues. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Accordiong to http://en.wikipedia.org/wiki/Amifostine, amifostine is a cytoprotective adjuvant used in cancer chemotherapy involving DNA-binding chemotherapeutic agents. Also commonly known as WR-1065 in its active form. It is marketed by MedImmune under the trade name Ethyol.

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 fact that amifostine could protect tumors could not be excluded. Given better treatment options for non-small cell lung cancer, this indication for non-small cell lung cancer was withdrawn in 2005.

Amifostine is an organic thiophosphate prodrug which is hydrolysed in vivo by alkaline phosphatase to the active cytoprotective thiol metabolite. 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 only be administered intravenously, after reconstitution with normal saline. Infusions lasting less than 15 minutes decrease the risk of adverse effects. The patient should be well-hydrated before administration.

Amifostine is a white crystalline powder which is freely soluble in water. Its empirical formula is C5H15N2O3PS and it has a molecular weight of 214.22. ETHYOL is the trihydrate form of amifostine and is supplied as a sterile lyophilized powder requiring reconstitution for intravenous infusion. Each single-use 10 mL vial contains 500 mg of amifostine on the anhydrous basis.

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