Captopril and losartan for mitigation of renal injury caused by single-dose total-body irradiation. Radiat Res 2011 Jan;175(1):29-36
Date
12/24/2010Pubmed ID
21175344Pubmed Central ID
PMC3080022DOI
10.1667/RR2400.1Scopus ID
2-s2.0-78650629415 (requires institutional sign-in at Scopus site) 69 CitationsAbstract
It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin 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 to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) "Animal Efficacy Rule", we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m(2)/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed.
Author List
Moulder JE, Cohen EP, Fish BLMESH terms used to index this publication - Major topics in bold
Angiotensin II Type 1 Receptor BlockersAngiotensin-Converting Enzyme Inhibitors
Animals
Azotemia
Captopril
Hypertension
Kidney
Linear Models
Losartan
Male
Proteinuria
Radiation Injuries
Rats
Renal Insufficiency
United States
United States Food and Drug Administration
Whole-Body Irradiation
