Pharmacokinetics of iron isomaltoside 1000 in patients with inflammatory bowel disease

Background: Iron isomaltoside 1000 is a novel injectable iron compound which offers potential advantages in the treatment of subjects with iron-deficiency anemia. We studied the pharmacokinetics (PK) of this novel compound in subjects with mild-to-moderate inflammatory bowel disease (IBD). Methods: This open-label, crossover, single-center trial was conducted in 12 subjects with IBD who were allocated to one of the two single intravenous (IV) bolus sequences of iron isomaltoside 1000: 100 mg followed by 200 mg, or vice-versa. PK variables were analyzed according to a single-compartment model. Results: The concentration-versus-time relationship for isomaltoside-bound iron (IBI) and total iron (TI) showed first-order kinetics with small deviations from dose-linearity. The area under the concentration-time curve (AUC) values in h * mu g/mL for IBI following 100 mg and 200 mg doses were 888 and 2141 respectively, and for TI following 100 mg and 200 mg doses, the AUC values were 1010 and 2319 respectively. The corresponding maximum serum concentration (C-max) values in mu g/mL were 35.6 and 68.6 for IBI, and 37.3 and 71.1 for TI. The half-life (T-1/2) values for IBI and TI were between 20.8-23.5 hours. The apparent volume of distribution (V-D) ranged from 3.0-3.5 L. Only approximately 1% of the doses administered were excreted in the urine. No serious adverse event (SAE) was reported. One subject was withdrawn after the 100 mg dose due to abdominal pain and flushing. Conclusion: At the administered doses, iron isomaltoside 1000 showed first-order PK, and did not raise safety concerns in patients with IBD. The PK parameters for IBI were close to those of TI.