TY - JOUR
T1 - The efficacy of oral deferiprone in acute iron poisoning
AU - Berkovitch, Matitiahu
AU - Livne, Amir
AU - Lushkov, Gili
AU - Segal, Michael
AU - Talmor, Clara
AU - Bentur, Yedidia
AU - Klein, Julia
AU - Koren, Gideon
N1 - Funding Information:
From the Departments of *Pediatrics, l-Pathology, and :~Biochemistry, Assaf Harofeh Medical Center, The Sackler School of Medicine, TeI-Aviv University, the §Israel Poison Information Center, Rambam Medical Center, Technion, Haifa, Israel, and the IIDivision of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Canada. Manuscript received November 4, 1998, returned January 24, 1999; revision received February 28, 1999, accepted March 21, 1999. Supported by Grant no. 3994/u from the Chief Scientist's Office, Ministry of Health, Israel, 1996. Address reprint requests to Dr Berkovitch, Department of Paediatrics, Assaf Harofeh Medical Center, Zerifin 70300, Israel. E-mail: mberkovitch @asaf.health.gov.il Key Words: Deferiprone, acute iron intoxication, rats. Copyright © 2000 by W.B. Saunders Company 0735-6757/00/1801-0008510.00/0
PY - 2000
Y1 - 2000
N2 - 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. Copyright (C) 2000 W.B. Saunders Company.
AB - 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. Copyright (C) 2000 W.B. Saunders Company.
KW - Acute iron intoxication
KW - Deferiprone
KW - Rats
UR - http://www.scopus.com/inward/record.url?scp=0033969435&partnerID=8YFLogxK
U2 - 10.1016/S0735-6757(00)90045-7
DO - 10.1016/S0735-6757(00)90045-7
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C2 - 10674529
AN - SCOPUS:0033969435
SN - 0735-6757
VL - 18
SP - 36
EP - 40
JO - American Journal of Emergency Medicine
JF - American Journal of Emergency Medicine
IS - 1
ER -