Plasma Pharmacokinetics of Two Consecutive Doses of Ferumoxytol in Healthy Subjects

Intravenous (IV) iron is used to treat iron-deficiency anemia in patients with chronic kidney disease (CKD). Ferumoxytol is a novel iron formulation administered rapidly as two IV boluses of 510 mg each. In this placebo-controlled, double-blind, parallel-group study, 58 healthy volunteers received ferumoxytol in two 510 mg doses administered 24 h apart. Population pharmacokinetics (PK) analysis was conducted, and a two-compartment open model with zero-order input and Michaelis-Menten elimination was found to best describe the data. The population mean estimates for volume of distribution of the central compartment (V-1), maximal elimination rate (V-max), and ferumoxytol concentration at which rate of metabolism would be one-half of V-max (K-m) were 2.71l, 14.3 mg/h, and 77.5 mg/l, respectively. When the effect of body weight on V-1 was added in the analysis, interindividual variability was found to be reduced. A noncompartmental analysis of two simulated 510-mg ferumoxytol doses was also performed to provide clinically interpretable data on half-life and exposure. Ferumoxytol given as two consecutive 510-mg doses was well tolerated.