Document Detail

Pharmacological properties of orally available, amphipathic polyaminocarboxylic acid chelators for actinide decorporation.
MedLine Citation:
PMID:  20699705     Owner:  NLM     Status:  MEDLINE    
Commonly used water-soluble polyaminocarboxylic acid (PACA) chelators, such as EDTA and DTPA, require intravenous or subcutaneous administration due to their poor bioavailability. The bioavailability of PACAs can be improved by the addition of differing lengths of alkyl side chains that alter amphipathic properties. Orally administered amphipathic triethylenetetramine pentaacetic acid (TT) compounds are efficacious for decorporation of plutonium and americium. The synthesis, efficacy, binding affinities, and some initial pharmacokinetics properties of amphipathic TT chelators are reviewed. C-labeled C12TT and C22TT chelators are reasonably well absorbed from the intestine and have a substantial biliary/fecal excretion pathway, unlike DTPA, which is mostly excreted in the urine. Whole body retention times are increased as a function of increasing lipophilicity. Neutron-induced autoradiography studies demonstrate that the oral administration of the chelators can substantially inhibit the redistribution of Pu in skeletal tissues. In summary, amphipathic TT-based chelators have favorable bioavailability, have a significant biliary excretion pathway, have demonstrated efficacy for americium and plutonium, and are thus good candidates for further development. Furthermore, some of the pharmacological properties can be manipulated by changing the lengths of the alkyl side chains and this may have some advantage for decorporation of certain metals and radionuclides.
Scott C Miller; Xuli Wang; Beth M Bowman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Health physics     Volume:  99     ISSN:  1538-5159     ISO Abbreviation:  Health Phys     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-11     Completed Date:  2010-10-25     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  2985093R     Medline TA:  Health Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  408-12     Citation Subset:  IM    
Division of Radiobiology, University of Utah, Salt Lake City, UT 84108, USA.
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MeSH Terms
Acetates / administration & dosage,  chemistry,  pharmacokinetics*,  pharmacology*
Administration, Oral
Americium / pharmacokinetics*,  toxicity
Biological Availability
Carbon Radioisotopes
Chelating Agents / administration & dosage,  chemical synthesis,  pharmacokinetics*,  pharmacology*
Decontamination / methods*
Intestinal Absorption / drug effects,  physiology
Pentetic Acid / chemistry,  pharmacology
Plutonium / pharmacokinetics*,  toxicity
Trientine / administration & dosage,  analogs & derivatives*,  chemistry,  pharmacokinetics,  pharmacology
Grant Support
Reg. No./Substance:
0/Acetates; 0/Carbon Radioisotopes; 0/Chelating Agents; 112-24-3/Trientine; 137203-80-6/docosyl-triethylenetetraminepentaacetic acid; 67-43-6/Pentetic Acid; 7440-07-5/Plutonium; 7440-35-9/Americium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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