Iron chelation using subcutaneous infusions of diethylene triamine penta‐acetic acid (DTPA)

Pippard, M. J.; Jackson, MJ; Hoffman, K.; Petrou, Mary; Modell, C. B.

doi:10.1111/j.1600-0609.1986.tb02282.x

Cited by 72 publications

(23 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the selectivity of these molecules for iron(III) is relatively poor. This lack of selectivity leads to zinc depletion in patients receiving aminocarboxylate‐based ligands such as DTPA [41] . Indeed cereals (e.g.…”

Section: Factors Considered When Designing Iron‐binding Macromoleculesmentioning

confidence: 99%

See 1 more Smart Citation

Design of clinically useful macromolecular iron chelators

Zhou

Winkelmann

Dai

et al. 2011

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Objectives In recent years, macromolecular iron chelators have received increasing attention as human therapeutic agents. The objectives of this article are: one, to discuss the factors which should be considered when designing iron binding macromolecules as human therapeutic agents, and two, to report recent achievements in the design and synthesis of appropriate macromolecular chelators that have resulted in the production of a number of agents with therapeutic potential. Key findings Macromolecular drugs exhibit unique pharmaceutical properties that are fundamentally different from their traditional small-molecule counterparts. By virtue of their high-molecular-weight characteristics, many are confined to extracellular compartments, for instance, the serum and the gastrointestinal tract. In addition, they have potential for topical administration. Consequently, these macromolecular drugs are free from many of the toxic effects that are associated with their low-molecular-weight analogues. Summary The design and synthesis of macromolecular iron chelators provides a novel aspect to chelation therapy. 3-Hydroxypyridin-4-one hexadentate-based macromolecular chelators have considerable potential for the development of new treatments for iron overload and for topical treatment of infection.

show abstract

Section: Factors Considered When Designing Iron‐binding Macromoleculesmentioning

confidence: 99%

“…This lack of selectivity leads to zinc depletion in patients receiving aminocarboxylate-based ligands such as DTPA. [41] Indeed cereals (e.g. wheat) synthesise such molecules in order to scavenge both iron and zinc from the soil.…”

Section: Thermodynamic Stability Of Iron(iii) Complexesmentioning

confidence: 99%

Design of clinically useful macromolecular iron chelators

Zhou

Winkelmann

Dai

et al. 2011

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

show abstract

“…DTPA strips metals other than iron (e.g., Zn), causing significant side effects (Pippard et al, 1986, Levien et al, 2005). In the case of the 3'- and 4'-polyether analogues, it was clear that although these ligands promoted the clearance of uranium, they were also excellent iron chelators.…”

Section: Resultsmentioning

confidence: 99%

“…or subcutaneous (s.c.) administration, and presents with a number of side effects associated with zinc stripping (Pippard et al, 1986, Levien et al, 2005). While parenterally administered chelators have a place, the lack of orally active ligands is of genuine concern in the case of mass exposure.…”

Section: Introductionmentioning

confidence: 99%

Desferrithiocin analogue uranium decorporation agents

Bergeron

Wiegand

Singh

2009

International Journal of Radiation Biology

View full text Add to dashboard Cite

Purpose Previous systematic structure-activity studies of the desferrithiocin (DFT) platform have allowed the design and synthesis of analogues and derivatives of DFT that retain the exceptional iron-clearing activity of the parent, while eliminating its adverse effects. We hypothesized that a similar approach could be adopted to identify DFT-related analogues that could effectively decorporate uranium. Materials and Methods The decorporation properties of nine DFT-related analogues were determined in a bile duct-cannulated rat model. Diethylenetriaminepentaacetic acid (DTPA) served as a positive control. Selected ligands also underwent multiple and delayed dosing regimens. Uranium excretion in urine and bile or stool was determined by inductively coupled plasma mass spectroscopy (ICP-MS); tissue levels of uranium were also assessed. Results The two best clinical candidates are (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE (9)], with a 57% reduction in kidney uranium levels on oral (p.o.) administration and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT-PE (10)], with a 62% renal reduction on p.o. administration. The majority of the metal excretion promoted by these analogues is in the bile, thus further reducing kidney actinide exposure. Conclusions While 9 administered p.o. or subcutaneously (s.c.) immediately post-metal is an effective decorporation agent, withholding the dose (s.c.) until 4 h reduced the activity of the compound. Conversion of 9 to its isopropyl ester may circumvent this issue.

show abstract

“…Potassium iodide is used to saturate the thyroid gland with stable iodine and prevent additional subsequent uptake of radioactive iodine (Kazzi et al, 2015). Ca-DTPA is usually recommended for an initial administration soon after intake owing to its higher efficacy; however, Zn-DTPA is preferred at later times because of its similar efficacy but lower toxicity (Pippard, Jackson, Hoffman, Petrou, & Modell, 1986;Taylor, Hodgson, & Stradling, 2007). In addition, i.v.…”

Section: Introductionmentioning

confidence: 99%

Developing a robust LC–MS/MS method to quantify Zn‐DTPA, a zinc chelate in human plasma and urine

Meng

Guo³

et al. 2018

Biomedical Chromatography

View full text Add to dashboard Cite

Quantitation of Zn-DTPA (zinc diethylenetriamene pentaacetate, a metal chelate) in complex biological matrix is extremely challenging on account of its special physiochemical properties. This study aimed to develop a robust and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of Zn-DTPA in human plasma and urine. The purified samples were separated on Proteonavi (250 × 4.6 mm, 5 μm; Shiseido, Ginza, Tokyo, Japan) and a C guard column. The mobile phase consisted of methanol-2 mm ammonium formate (pH 6.3)-ammonia solution (50:50:0.015, v/v/v), flow rate 0.45 mL/min. The linear concentration ranges of the calibration curves for Zn-DTPA were 1-100 μg/mL in plasma and 10-2000 μg/mL in urine. The intra- and inter-day precisions for quality control (QC) samples were from 1.8 to 14.6% for Zn-DTPA and the accuracies for QC samples were from -4.8 to 8.2%. This method was fully validated and successfully applied to the quantitation of Zn-DTPA in plasma and urine samples of a healthy male volunteer after intravenous infusion administration of Zn-DTPA. The result showed that the concentration of Zn-DTPA in urine was about 20 times that in plasma, and Zn-DTPA was completely (94.7%) excreted through urine in human.

show abstract

Iron chelation using subcutaneous infusions of diethylene triamine penta‐acetic acid (DTPA)

Cited by 72 publications

References 15 publications

Design of clinically useful macromolecular iron chelators

Design of clinically useful macromolecular iron chelators

Desferrithiocin analogue uranium decorporation agents

Developing a robust LC–MS/MS method to quantify Zn‐DTPA, a zinc chelate in human plasma and urine

Contact Info

Product

Resources

About