Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

Table 1 Comparison of the main available iron chelators to an ideal chelation drug (modified from 2469)

	"Ideal chelator"	Deferoxamine	Deferiprone	Deferasirox
Route of administration	Oral	Parenteral, usually subcutaneous or intravenous	Oral	Oral
Plasma half-life	Long enough to give constant protection from labile plasma iron	Short (minutes); requires constant delivery	Moderate (< 2 hours). Requires at least 3-times-per-day dosing	Long, 8–16 hours; remains in plasma at 24 h
Therapeutic index	High	High at moderate doses in iron-overloaded subjects	Idiosyncratic side effects are most important	Probably high in iron overloaded subjects*
Molar iron chelating efficiency; charge of iron (III) complex	High, uncharged	High (hexadentate); charged	Low (bidentate); uncharged	Moderate (tridentate); uncharged
Important side effects	None or only in iron-depleted subjects	Auditory and retinal toxicity; effects on bones and growth; potential lung toxicity, all at high doses; local skin reactions at infusion sites	Rare but severe agranulocytosis; mild neutropenia; common abdominal discomfort; erosive arthritis	Abdominal discomfort; rash or mild diarrhoea upon initiation of therapy; mild increased creatinine level
Ability to chelate intracellular cardiac and other tissue iron in humans	High	Probably lower than deferiprone and deferasirox (it is not clear why)	High in clinical and in in vitro studies	Insufficient clinical data available; promising in laboratory studies

*Nephrotoxicity that has been observed in non-iron-loaded animals has been minimal in iron-overloaded humans, but effectiveness is demonstrated only at higher end of tested doses, as discussed in 1693.

ISSN: 1755-8794