Ferumoxytol metabolism is not dependent on renal function. It is removed from the circulation by the reticuloendothelial system of the liver, spleen, and bone marrow. Iron, bound to transferrin, is then transported in the plasma and distributed to the bone marrow for the synthesis of hemoglobin, to the reticuloendothelial system for storage, and to all cells for enzymes containing iron, and to placental cells if needed to meet fetal needs. Transferrin eventually becomes available for recycling. In normal adults, 90% of metabolized iron is conserved and reutilized repeatedly.
The iron in Feridex i.v. enters the normal body iron metabolism cycle as evidenced by transient increases in serum iron values one day after administration and increase in serum ferritin values 7 days after administration. The amount of iron contained in a single dose is 39 mg for a 70 kg individual. This is less than 1/5 the amount of iron contained in one unit of whole blood.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
◉ Summary of Use during Lactation:Ferumoxides is a complex of iron oxide and dextran, similar to iron dextran. It is not expected to pose a toxic risk to a nursing infant. However, because there is no published experience with ferumoxides during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
Bioavailability studies were not conducted as ferumoxytol has been developed for IV administration only. Iron therapy dosage is individualized according to specific goals for blood iron concentrations, iron storage parameters (e.g., ferritin, transferrin saturation), and serum hemoglobin concentrations. Iron toxicity is possible with excessive or unnecessary iron therapy. Systemic iron is stored in ferritin and hemosiderin, which are utilized for future production of hemoglobin. The absorption of iron depends on the route of administration. The tissue that first clears parenterally ingested iron from the plasma determines its bioavailability. If the reticuloendothelial system clears iron effectively, only small amounts will become available over time to the bone marrow. Transferrin accepts iron from the intestinal tract and also from sites of hemoglobin storage and destruction.
The population mean estimates for volume of distribution of the central compartment (V(1)), maximum 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/hr, and 77.5 mg/L, respectively.
Three healthy, adult male volunteers received a dose of Feridex I.V. 0.56 mg of Fe/kg (diluted in 100 mL of 5% dextrose and intravenously infused over 30 minutes). In these subjects, the mean +/- SD peak serum iron concentration was 5.5 +/- 0.6 ug/mL and total clearance 28.5 +/- 1.6 mL/min.
