Efficacy of deferiprone in the treatment of acute iron intoxication in rats.
BACKGROUND
Deferiprone [(1,2-dimethyl-3-hydroxypyrid-4-one) (L1)], is the first orally active iron chelating agent to reach clinical trials in patients with chronic iron overload. Its efficacy in preventing morbidity and mortality in acute iron poisoning has not been tested.


OBJECTIVE
To determine whether deferiprone can reduce the mortality of rats following toxic oral doses of iron.


METHODS
Rats were administered 612 mg/kg elemental iron by gavage, corresponding to the LD58. A parallel group received the same oral dose of iron followed by deferiprone intraperitoneally at 400 mg/kg (loading dose), followed by additional intraperitoneal injections of 200 mg/kg, 100 mg/kg and 100 mg/kg of deferiprone at one hour intervals.


RESULTS
Coadministering deferiprone with the iron decreased mortality from 58% (11/19) to 15% (3/20) (p = 0.013). The administration of deferiprone was associated with urinary excretion of iron (which did not occur with iron alone) and the production of the red deferiprone-iron complex. On histological examination there appeared to be less iron in the liver and gastrointestinal tract.


CONCLUSIONS
The coadministration of deferiprone can decrease morbidity and mortality caused by acute iron overdose. Deferiprone holds promise for the treatment of iron poisoning but additional study is required.
Fassos
F F
FF
Hospital for Sick Children, Toronto, Ontario, Canada.
Berkovitch
M
M
Daneman
N
N
Koren
L
L
Cameron
R G
RG
Klein
J
J
Falcitelli
C
C
St Louis
P
P
Daneman
R
R
Koren
G
G
D000818:Animals; D000077543:Deferiprone; D004386:Duodenum / Q000737:chemistry; D007274:Injections, Intraperitoneal; D007501:Iron / Q000378:metabolism / Q000506:poisoning*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D011041:Poisoning / Q000188:drug therapy / Q000401:mortality; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000737:chemistry; D015996:Survival Rate; D014018:Tissue Distribution
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D007501:Iron