Pharmacokinetic study of ferumoxytol: a new iron replacement therapy in normal subjects and hemodialysis patients.
BACKGROUND
Currently available intravenous iron preparations are not ideal, either because of safety concerns or dose limitations. We investigated the safety and pharmacokinetics of ferumoxytol, a new iron replacement therapy, in normal subjects and hemodialysis patients.


METHODS
In a randomized, double-blind, ascending-dose study in normal volunteers (n = 41), 6 subjects received placebo, and 8 subjects each received ferumoxytol, at 1, 2 or 4 mg iron/kg, injected at 60 mg iron/min. The remaining subjects received 4 mg iron/kg at injection rates of 90 (n = 3), 180 (n = 3) or 1,800 mg iron/min (n = 5). In the second, open-label, ascending-dose study, 20 hemodialysis patients received 125 or 250 mg of iron over 5 min.


RESULTS
In normal subjects, the blood half-life of ferumoxytol increased with increasing dose from 9.3 to 14.5 h (p < 0.05) but not with increasing rate of injection. The drug half-life in hemodialysis patients was similar to normal subjects. Ferumoxytol was not removed with hemodialysis. Serum iron (p < 0.001), transferrin saturation (p < 0.001) and ferritin increased in both populations. No serious adverse events were attributable to ferumoxytol.


CONCLUSIONS
Ferumoxytol was well tolerated in this study. Its pharmacokinetic properties and simplicity of administration suggest that it will be an attractive form of iron replacement therapy.
Landry
Robert
R
Division of Nephrology, University of Virginia Health System, Charlottesville, USA.
Jacobs
Paula M
PM
Davis
Robert
R
Shenouda
Magdy
M
Bolton
W Kline
WK
D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D016896:Treatment Outcome
D006397:Hematinics; D004921:Erythropoietin