Drug Groups

approved; investigational

Description

A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [PubChem]

Indication

For reduction in the cumulative renal toxicity in patients with ovarian cancer (using cisplatin) and moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer.

Pharmacology

Amifostine is an organic thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer or non-small cell lung cancer and also to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer. Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite, believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumour cells.

Toxicity

Rat LD₅₀: 826 mg/kg

Affected Organisms

Biotransformation

Amifostine is rapidly dephosphorylated by alkaline phosphatase in tissues primarily to the active free thiol metabolite and, subsequently, to a less active disulfide metabolite.

Half Life

8 minutes

Elimination

After a 10-second bolus dose of 150 mg/m2 of ETHYOL, renal excretion of the parent drug and its two metabolites was low during the hour following drug administration, averaging 0.69%, 2.64% and 2.22% of the administered dose for the parent, thiol and disulfide, respectively.

References

External Links