Pharmacokinetic Study of Ferumoxytol: A New Iron Replacement Therapy in Normal Subjects and Hemodialysis Patients

Abstract

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. Conclusion: 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.

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study

“…In plasma, the elimination half-life of FMX was 22.1 hours (n ¼ 14; 95% CI, 19.7-24.5; Fig. 3C), consistent with previously published data in healthy subjects (36,37) and comparable with the reported half-life of nal-IRI (11,35). Plasma exposure (AUC 0!t ) for FMX and nal-IRI were correlated (r ¼ 0.7528; P ¼ 0.0030).…”

“…Other pharmacokinetic parameters for FMX are summarized in Supplementary Table S2. Metabolic turnover of FMX resulted in elevated plasma ferritin levels as described previously (29,36). Ferritin levels in plasma increased from a median concentration of 267 ng/mL (range, 45-1,481 ng/mL) during patient screening to 691 ng/mL (range, 430-1,730 ng/mL) at day 4 after FMX injection.…”

“…FMX degradation (44,47) will result in a corresponding decrease in the R2 Ã signal, as the magnetic moment of ferritin is far smaller than that of FMX. Compartmentalization of iron oxide particles after phagocytic uptake into macrophages can double R2 Ã (48, 49) and may thus counteract any loss of signal due to partial degradation of FMX particles during the imaging period (36,44,47). The effects of compartmentalization may also lead to an overestimation of FMX levels particularly at late time points, although this error contribution is thought to be relatively uniform across a patient population.…”

Physicochemical Characterization of Nebulized Superparamagnetic Iron Oxide Nanoparticles (SPIONs)

“…The iron is then released intracellularly within vesicles in macrophages where it can bind to ferritin or incorporate into hemoglobin. (20) Although the physical, pharmacokinetic, and biologic properties of ferumoxytol in therapeutic trials have been reported for IV injection, (21) the authors are not aware of physicochemical characterization conducted on nebulized Rienso.…”

Evaluation of renal quantitative T2* changes on MRI following administration of ferumoxytol as a T2* contrast agent

“…The blood half-life is dose-dependent and is approximately 14.5 hours at a dose of 4 mg/kg. 7 All subjects received ferumoxytol intravenously at a dose of 4 mg/kg (group A, n=12) or 6 mg/kg (group B, n=12) to a maximum dose of 510 mg of elemental iron.…”