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 2.71 l, 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.

RCT Entities:   Population Interventions Outcomes