A comparison of the iron-clearing properties of 1,2-dimethyl-3-hydroxypyrid-4-one, 1,2-diethyl-3-hydroxypyrid-4-one, and deferoxamine.
A comparative study of the iron-clearing properties of subcutaneously (SC) administered deferoxamine (DFO) with those of orally administered 1,2-dimethyl-3-hydroxypyrid-4-one (CP20) and 1,2-diethyl-3-hydroxypyrid-4-one (CP94) is presented. The studies were performed in both a non-iron-overloaded, bile duct-cannulated rat model and an iron-loaded Cebus monkey model. All three drugs performed well in the rodent, promoting the excretion of iron in both the urine and the bile, with total iron output efficiencies of 2.8%, 1.2%, and 7.1%, respectively. The efficiency of DFO increased slightly in the Cebus model, while that of the hydroxypyridones was essentially the same in the monkey, with total iron output efficiencies of 5.5%, 2.1%, and 7.4%, respectively. Iron balance studies showed that both DFO and CP94 were able to maintain the animals in a negative iron balance, while CP20 had little impact.
Bergeron
R J
RJ
University of Florida, College of Pharmacy, Department of Medical Chemistry, Gainesville 32610.
Streiff
R R
RR
Wiegand
J
J
Luchetta
G
G
Creary
E A
EA
Peter
H H
HH
D000818:Animals; D001646:Bile / Q000378:metabolism; D002428:Cebus; D000077543:Deferiprone; D003676:Deferoxamine / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D007501:Iron / Q000378:metabolism* / Q000652:urine; D007502:Iron Chelating Agents / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011728:Pyridones / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D007502:Iron Chelating Agents; D011728:Pyridones; C068543:1,2-diethyl-3-hydroxypyridin-4-one; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine