The efficacy of oral deferiprone in acute iron poisoning.
Due to its high cost and need for parenteral administration, the standard iron chelator deferoxamine is not used in many individuals with acute and chronic iron poisoning worldwide. Deferiprone is the first oral iron chelator to be shown to be effective in chronically iron overloaded thalassemia patients. Its efficacy, by oral administration, in acute iron poisoning has not been tested. Our objective was to determine whether orally administered deferiprone can reduce the mortality of rats following acute, toxic, oral doses of iron. Rats were administered 612 mg/kg elemental iron orally, corresponding to LD50 in the species tested. Two other groups received the same oral dose of iron followed by oral deferiprone: 800 mg/kg and 800 mg/kg, followed by another dose of 800 mg/kg 2 hours later. Coadministration of 800 mg/kg deferiprone with the iron decreased mortality from 30% to 6.6% after 2 hours (P = .02), from 40% to 16.6% after 12 hours (P = .04), and from 53.3% to 20% after 24 hours (P = 0.007). Mortality was also significantly decreased among animals coadministrated 2 repeated doses of deferiprone of 800 mg/kg with iron, to 0%, 9%, and 18%, and 2, 12, and 24 hours postdrug administration, respectively (P = .04, .05, .04, respectively). Histologically, there was a dose-dependent decrease in iron accumulation in the gastrointestinal tract. Orally administered deferiprone can decrease morbidity and mortality caused by acute iron overdose in rats. Oral deferiprone holds promise in the treatment of iron poisoning in humans.
Berkovitch
M
M
Department of Pediatrics, Assaf Harofeh Medical Center, The Sackler School of Medicine, Tel-Aviv University, Zerifin, Israel. mberkovitch@asaf.health.gov.il
Livne
A
A
Lushkov
G
G
Segal
M
M
Talmor
C
C
Bentur
Y
Y
Klein
J
J
Koren
G
G
D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D000077543:Deferiprone; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007501:Iron / Q000506:poisoning*; D007502:Iron Chelating Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007928:Lethal Dose 50; D008297:Male; D009017:Morbidity; D011041:Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011728:Pyridones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D013997:Time Factors; D014018:Tissue Distribution
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D007501:Iron