Treatment for Actinide-bearing Industrial Dusts and Aerosols

Stradling, G.N.; Taylor, David; Hengé-Napoli, M. H.; Wood, Roger; Silk, T J

doi:10.1093/oxfordjournals.rpd.a032978

Cited by 9 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhalation route of contamination was chosen in this decorporation study to mimic the route of contamination that may occur in a real‐life scenario. Contamination with 241 Am nitrate is a realistic hazard and the chemical complex is a moderately soluble form that can slowly release from the lung and into the systemic circulation . Administering the prodrug 1 h after contamination resulted in an 11‐fold decrease in liver accumulation compared with the control treatment in this study.…”

Section: Discussionmentioning

confidence: 61%

“…The rate of systemic entry depends on the route of contamination and the properties of the radionuclide, including solubility, charge, and chemical form . Incorporation via inhalation and wound are considered to be the two of the most probable routes of radionuclide contamination and are characterized as exhibiting slow or protracted entry of the contaminant into the bloodstream . Unless frequent injections or continuous infusion of DTPA are administered, its rapid elimination could quickly deplete the available DTPA in the blood and allow for only a limited duration of efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…25,26 Incorporation via inhalation and wound are considered to be the two of the most probable routes of radionuclide contamination and are characterized as exhibiting slow or protracted entry of the contaminant into the bloodstream. 9,27,28 Unless frequent injections or continuous infusion of DTPA are administered, its rapid elimination could quickly deplete the available DTPA in the blood and allow for only a limited duration of efficacy. Accordingly, alternative delivery methods with both DTPA and DTPA penta-ethyl ester have been proposed.…”

Section: Discussionmentioning

confidence: 99%

“…As an established decorporation agent, DTPA is maintained in the United States Strategic National Stockpile (SNS) in case of radiological and nuclear emergencies. Its efficacy against 241 Am contamination has been proven mostly in controlled decorporation studies with animal models . Rats and beagles represent the most commonly used animal models, and 30 μmol/kg has been established as the standard human dose.…”

Section: Introductionmentioning

confidence: 99%

“…Its efficacy against 1564 RESEARCH ARTICLE -Pharmacokinetics, Pharmacodynamics and Drug Transport and Metabolism 241 Am contamination has been proven mostly in controlled decorporation studies with animal models. 8,9 Rats and beagles represent the most commonly used animal models, and 30 :mol/kg has been established as the standard human dose. A single i.v.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Orally Administered DTPA Penta-Ethyl Ester for the Decorporation of Inhaled 241Am

Sueda

Sadgrove

Huckle

et al. 2014

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Diethylenetriaminepentaacetic acid (DTPA) is an effective decorporation agent to facilitate the elimination of radionuclides from the body, but its permeability-limited oral bioavailability limits its utility in mass-casualty emergencies. To overcome this limitation, a prodrug strategy using the penta-ethyl ester form of DTPA is under investigation. Pharmacokinetic and biodistribution studies were conducted in rats by orally administering [14C]DTPA penta-ethyl ester, and this prodrug and its hydrolysis products were analyzed as a single entity. Compared to a previous reporting of intravenously administered DTPA, the oral administration of this prodrug resulted in a sustained plasma concentration profile with higher plasma exposure and lower clearance. An assessment of the urine composition revealed that the bioactivation was extensive but incomplete, with no detectable levels of the penta- or tetra-ester forms. Tissue distribution at 12 h was limited, with approximately 73% of the administered dose being associated with the gastrointestinal tract. In the efficacy study, rats were exposed to aerosols of 241Am nitrate before receiving a single oral treatment of the prodrug. The urinary excretion of 241Am was found to be 19% higher than with the control. Consistent with prior reports of DTPA, the prodrug was most effective when the treatment delays were minimized.

show abstract

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%