title: Preclinical studies on the radioprotective efficacy and pharmacokinetics of subcutaneously administered amifostine.
abstract: The radioprotective effects and pharmacokinetics of subcutaneously (SC) administered amifostine have been investigated in animal studies. Studies in rats using a single dose of amifostine showed that SC administration gave protection from radiation-induced mucositis that is at least equivalent to that achieved by intravenous administration of the drug. These studies also indicate that tissue levels of the active metabolite WR-1065 correlated better with the radioprotective effects of amifostine than do plasma WR-1065 levels. Multiple-dose studies in rats show radioprotective effects equal to or greater than those obtained with intravenous dosing in the setting of fractionated irradiation. In addition, there is no evidence of drug accumulation in either normal or tumor tissue, with tumor WR-1065 levels peaking just above the limits of quantitation during treatment. Preliminary data from studies of SC amifostine in monkeys indicate a plasma pharmacokinetic profile similar to that reported earlier in humans. Tissue WR-1065 levels were higher at 30 minutes after SC dosing than they were after intravenous dosing and were comparable for the two routes at 60 minutes.
authors.affiliation: Department of Molecular Biology/Biochemistry, MedImmune, Inc, Gaithersburg, MD 20878, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Cassatt
authors.forename: Christine A
authors.initials: CA
authors.lastname: Fazenbaker
authors.forename: Gizachew
authors.initials: G
authors.lastname: Kifle
authors.forename: Christine M
authors.initials: CM
authors.lastname: Bachy
mesh_terms: D004999:Amifostine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D019610:Cytoprotection; D004353:Drug Evaluation, Preclinical; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D008624:Mercaptoethylamines / Q000378:metabolism; D011832:Radiation Injuries / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats
chemical_list: D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D004999:Amifostine