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Updated: Aug 19, 2026
Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction
Published on: April 24, 2016
Amifostine (ETHYOL) protects rats from mucositis resulting from fractionated or hyperfractionated radiation exposure
David R Cassatt1, Christine A Fazenbaker, Christine M Bachy
1Department of Molecular Biology/Biochemistry, MedImmune Inc. One MedImmune Way, Gaithersburg, MD 20878, USA.
Purpose:
The cytoprotective drug amifostine (Ethyol) protects rats from oral mucositis resulting from a single dose of gamma-irradiation. We expanded earlier studies to determine whether multiple doses of amifostine protect against fractionated or hyperfractionated radiation and whether the active metabolite of amifostine (WR-1065) accumulates in tissues upon repeated administration.
Methods And Materials:
Rats received amifostine daily for 5 days in conjunction with a 1-week fractionated radiation schedule and were evaluated for oral mucositis. Rats also received amifostine before the am or pm exposure or b.i.d. in conjunction with hyperfractionated radiation. To determine the pharmacokinetics of WR-1065 after repeated dosing, amifostine was given 5 days a week for 1 or 3 weeks, and rat tissue and plasma were collected at intervals during and after treatment and analyzed for WR-1065.
Results:
Amifostine protected rats from mucositis resulting from fractionated or hyperfractionated radiation. When the number of days of amifostine administration was reduced, protection was diminished. A dose of 100 mg/kg given in the morning or 2 doses at 50 mg/kg provided the best protection against hyperfractionated radiation. WR-1065 did not accumulate in tissues or tumor upon repeated administration.
Conclusions:
Amifostine prevented radiation-induced mucositis in a rat model; protection was dose and schedule dependent.
