Captopril and Losartan for Mitigation of Renal Injury Caused by Single-Dose Total-Body Irradiation

• DOI: 10.1667/rr2400.1
• Publication Date: 2010-10-26T13:39:06Z
• Authors: John E. Moulder; Eric P. Cohen; Brian L. Fish
• Keywords: Captopril; Animal studies; Losartan Potassium

It is known that angiotensin converting enzyme inhibitors (ACEIs) and II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable the development agents mitigation injuries caused by terrorism-related radiation exposure. As part an effort develop animal model would fit requirements U.S. Food Drug Administration (FDA) "Animal Efficacy Rule", we designed new studies which FDA-approved ACEI (captopril) or ARB (losartan, Cozaar®) started 10 days after single total-body irradiation (TBI) at drug doses equivalent (on g/m(2)/day basis) prescribed humans. Captopril losartan were equally effective as mitigators, with DMFs 1.23 1.21, respectively, delaying failure. These show nephropathy in realistic rodent mitigated relevant agents. This lays necessary groundwork pivotal under FDA Animal Rule provides outline how FDA-required large-animal could designed.