Orally administered DTPA di-ethyl ester for decorporation of (241)Am in dogs: Assessment of safety and efficacy in an inhalation-contamination model.

Autor: Huckle JE; University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Division of Molecular Pharmaceutics , Chapel Hill , NC., Sadgrove MP, Pacyniak E, Leed MG, Weber WM, Doyle-Eisele M, Guilmette RA, Agha BJ, Susick RL, Mumper RJ, Jay M
Jazyk: angličtina
Zdroj: International journal of radiation biology [Int J Radiat Biol] 2015 Jul; Vol. 91 (7), pp. 568-75. Date of Electronic Publication: 2015 May 21.
DOI: 10.3109/09553002.2015.1043753
Abstrakt: Purpose: Currently two injectable products of diethylenetriaminepentaacetic acid (DTPA) are U.S. Food and Drug Administration (FDA)-approved for decorporation of (241)Am; however, an oral product is considered more amenable in a mass casualty situation. The di-ethyl ester of DTPA, named C2E2, is being developed as an oral drug for treatment of internal radionuclide contamination.
Materials and Methods: Single-dose decorporation efficacy of C2E2 administered 24-h post contamination was determined in beagle dogs using a (241)Am nitrate inhalation contamination model. Single and multiple dose toxicity studies in beagle dogs were performed as part of an initial safety assessment program. In addition, the genotoxic potential of C2E2 was evaluated by the in vitro bacterial reverse mutation Ames test, mammalian cell chromosome aberration cytogenetic assay and an in vivo micronucleus test.
Results: Oral administration of C2E2 significantly increased (241)Am elimination over untreated controls and significantly reduced the retention of (241)Am in tissues, especially liver, kidney, lung and bone. Daily dosing of 200 mg/kg/day for 10 days was well tolerated in dogs. C2E2 was found to be neither mutagenic or clastogenic.
Conclusions: The di-ethyl ester of DTPA (C2E2) was shown to effectively enhance the elimination of (241)Am after oral administration in a dog inhalation-contamination model and was well tolerated in toxicity studies.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje