ABSTRACT
BACKGROUND: Ferumoxytol is approved for the treatment of iron-deficiency anaemia (IDA) in adult patients with chronic kidney disease (CKD). Ferumoxytol has recently been investigated for use in all-cause IDA. This analysis was employed to bridge ferumoxytol pharmacokinetics (PK) across populations of healthy subjects and patients with CKD on haemodialysis, and to then make informed inferences regarding the PK behaviour of ferumoxytol in the all-cause IDA population. METHODS: The data analysis was performed using NONMEM. Selected parameters were included for covariate testing. Investigations to determine if changes in volume of distribution during haemodialysis improved the model fit were also conducted. The final model was used to simulate PK in healthy volunteers (HVs) and CKD patients with and without haemodialysis. RESULTS: The final model was a two-compartment model with non-linear elimination. During haemodialysis, the central volume V1 was estimated to be reduced by 0.198 L/h. A positive relationship was identified between initial V1 and observed weight loss during haemodialysis. V1 increased by 0.614 % per kilogram of body weight, and females had an 18.3 % lower V1 than males. Differences between simulated profiles for different populations were marginal: maximum concentration (Cmax) of 209 vs. 204 ng/mL and area under the curve from time zero to infinity (AUCinf) of 5,980 vs. 5,920 ng·h/mL in HVs and CKD non-haemodialysis patients, respectively, for a single dose of 510 mg. CONCLUSIONS: The results indicate that ferumoxytol PK are comparable between HVs and CKD patients. Furthermore, the results are representative of the PK in other populations and can be used to bridge to subjects with general IDA.
