Pharmacokinetics of Iron Isomaltoside1000 in Patients with Stage 5 Chronic Kidney Disease on Dialysis Therapy

Background: Iron deficiency anemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on dialysis. We investigated the pharmacokinetics, pharmacodynamics, and safety of three doses (100 mg, 200 mg, and 500 mg) of iron isomaltoside 1000administered as bolus injections in patients with stage 5 chronic kidney disease on dialysis therapy. Methods: This prospective, randomized, open-label pharmacokinetic study was conducted in 18 patients at one center. Patients were randomly assigned in a 1:1:1 ratio to receive a single dose of 100 mg, 200 mg, or 500 mg intravenous bolus injection (6 patients each) of iron isomaltoside 1000 at baseline visit. The pharmacokinetic, pharmacodynamics, and safety parameters were assessed over seven days and increases in serum-iron was used as a surrogate for iron isomaltoside 1000. Results: There was a dose-dependent increase in the geometric mean values of area under serum concentration-time curve (AUC) from injection to last measurable data point, area under serum concentration-time curve from injection to infinity (AUC0-t), and maximum serum concentration (Cmax), whereas time to reach maximum concentration (Tmax) decreased with increasing doses of iron isomaltoside 1000. Thegeometric mean of half-life (T½) was approximately 30 h and the elimination rate constant (Ke) remained similar across the three doses. Serum-iron, transferrin saturation, and serum-ferritin increased significantly, and the increases were related to iron dose. No major change was observed in the mean hemoglobin, reticulocyte count, reticulocyte hemoglobin content, ortotal iron binding capacity across the three doses. Three adverse events occurred of which one, asthma exacerbation, was considered probably related to the treatment. Conclusions: The pharmacokinetic characteristics and simplicity of administration of iron isomaltoside 1000 suggest it to be a convenient iron replacement therapy over this dosage range.