A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications
Abstract
The treatment of iron deficiency anemia with polynuclear iron formulations is an established therapy in patients with chronic kidney disease but also in other disease areas like gastroenterology, cardiology, oncology, pre/post operatively and obstetrics' and gynecology. Parenteral iron formulations represent colloidal systems in the lower nanometer size range which have traditionally been shown to consist of an iron core surrounded by a carbohydrate shell. In this publication, we for the first time describe the novel matrix structure of iron isomaltoside 1000 which differs from the traditional picture of an iron core surrounded by a carbohydrate. Despite some structural similarities between the different iron formulations, the products differ significantly in their physicochemical properties such as particle size, zeta potential, free and labile iron content, and release of iron in serum. This study compares the physiochemical properties of iron isomaltoside 1000 (Monofer) with the currently available intravenous iron preparations and relates them to their biopharmaceutical properties and their approved clinical applications. The investigated products encompass low molecular weight iron dextran (CosmoFer), sodium ferric gluconate (Ferrlecit), iron sucrose (Venofer), iron carboxymaltose (Ferinject/Injectafer), and ferumoxytol (Feraheme) which are compared to iron isomaltoside 1000 (Monofer). It is shown that significant and clinically relevant differences exist between sodium ferric gluconate and iron sucrose as labile iron formulations and iron dextran, iron carboxymaltose, ferumoxytol, and iron isomaltoside 1000 as stable polynuclear formulations. The differences exist in terms of their immunogenic potential, safety, and convenience of use, the latter being expressed by the opportunity for high single-dose administration and short infusion times. Monofer is a new parenteral iron product with a very low immunogenic potential and a very low content of labile and free iron. This enables Monofer, as the only IV iron formulation, to be administered as a rapid high dose infusion in doses exceeding 1000 mg without the application of a test dose. This offers considerable dose flexibility, including the possibility of providing full iron repletion in a single infusion (one-dose iron repletion).
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The rationale for the design of Iron isomaltoside 1000 was based on the "theoretically reduced anaphylactogenic potential" of the ligand.
“Notably, the rationale for the design of Iron isomaltoside 1000 was based on the “theoretically reduced anaphylactogenic potential” of the ligand [14,15].”
Cites
Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency
Anker, S. D., Comin Colet, J., Filippatos, G., Willenheimer, R., Dickstein, K., Drexler, H., Lüscher, T. F., Bart, B., Banasiak, W., Niegowska, J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0908355 · Cited by 2,083 · see citing works
Carter, P. M. (1971) · Analytical Biochemistry · doi:10.1016/0003-2697(71)90405-2 · Cited by 787 · see citing works
Update on adverse drug events associated with parenteral iron
Chertow, G. M., Mason, P. D., Vaage-Nilsen, O., & Ahlmén, J. (2005) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfi253 · Cited by 457 · see citing works
FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease
Lu, M., Cohen, M. H., Rieves, D., & Pazdur, R. (2010) · American Journal of Hematology · doi:10.1002/ajh.21656 · Cited by 443 · see citing works
Serious Hazards of Transfusion: A Decade of Hemovigilance in the UK
Stainsby, D., Jones, H., Asher, D., et al. (2006) · Transfusion Medicine Reviews · doi:10.1016/j.tmrv.2006.05.002 · Cited by 347 · see citing works
Characterization and application of FerroZine iron reagent as a ferrous iron indicator
Gibbs, C. R. (1976) · Analytical Chemistry · doi:10.1021/ac50002a034 · Cited by 291 · see citing works
A Conformational Study of Hydroxymethyl Groups in Carbohydrates Investigated by 1H NMR Spectroscopy
Bock, K., & Duus, J. Ø. (1994) · Journal of Carbohydrate Chemistry · doi:10.1080/07328309408011662 · Cited by 273 · see citing works
Self-citationParenteral iron therapy options
Silverstein, S. B., & Rodgers, G. M. (2004) · American Journal of Hematology · doi:10.1002/ajh.20056 · Cited by 217 · see citing works
Structure, chemistry, and pharmacokinetics of intravenous iron agents.
Danielson, B. G. (2004) · PubMed · doi:10.1097/01.asn.0000143814.49713.c5 · Cited by 208 · see citing works
Parenteral iron formulations: A comparative toxicologic analysis and mechanisms of cell injury
Zager, R. A., Johnson, A. C. M., Hanson, S. Y., & Wasse, H. (2002) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2002.33917 · Cited by 208 · see citing works
Rao, M. K. (2009) · Kidney International · doi:10.1038/ki.2009.19 · Cited by 172 · see citing works
Structure/histotoxicity relationship of parenteral iron preparations.
Geisser, P., Baer, M., & Schaub, E. (1992) · PubMed · Cited by 154 · see citing works
On the relative safety of parenteral iron formulations
Chertow, G. M., Mason, P. D., Vaage-Nilsen, O., & Ahlmén, J. (2004) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfh185 · Cited by 149 · see citing works
Physicochemical properties of ferumoxytol, a new intravenous iron preparation
Balakrishnan, V. S., Rao, M., Kausz, A. T., Brenner, L., Pereira, B. J. G., Frigo, T. B., & Lewis, J. M. (2009) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2009.02130.x · Cited by 144 · see citing works
Parenteral iron nephrotoxicity: Potential mechanisms and consequences1
Zager, R. A., Johnson, A. C. M., & Hanson, S. Y. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.00716.x · Cited by 136 · see citing works
Suspected iron dextran-related adverse drug events in hemodialysis patients
Fletes, R., Lazarus, J. M., Gage, J. O., & Chertow, G. M. (2001) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(01)80123-2 · Cited by 135 · see citing works
Múñoz, M., Breymann, C., García‐Erce, J. A., Gómez‐Ramírez, S., Colet, J. C., & Bisbe, E. (2007) · Vox Sanguinis · doi:10.1111/j.1423-0410.2007.01014.x · Cited by 117 · see citing works
Polymer Characterization by Liquid Chromatography
(1987) · Journal of chromatography library · doi:10.1016/s0301-4770(08)x6063-4 · Cited by 112 · see citing works
The Comparative Safety of Intravenous Iron Dextran, Iron Saccharate, and Sodium Ferric Gluconate
Fishbane, S., & Kowalski, E. A. (2000) · Seminars in Dialysis · doi:10.1046/j.1525-139x.2000.00104.x · Cited by 106 · see citing works
Booy, M. P. W. M. T., de Ruiter, R. A., & de Meere, A. L. J. (1992) · Pharmaceutical Research · doi:10.1023/a:1018944113914 · Cited by 98 · see citing works
Kudasheva, D. S., Lai, J., Ulman, A., & Cowman, M. K. (2004) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2004.06.010 · Cited by 84 · see citing works
Ljungström, K. G., Renck, H., Hédin, H., et al. (1983) · PubMed · Cited by 80 · see citing works
Breymann, Richter, Hüttner, et al. (2000) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2000.00605.x · Cited by 79 · see citing works
Revised recommendations for the measurements of the serum iron in human blood
Iron Panel of the International Committee for Standardization in Haematology (1990) · British Journal of Haematology · doi:10.1111/j.1365-2141.1990.tb07808.x · Cited by 73 · see citing works
Intravenous iron in inflammatory bowel disease
Múñoz, M., Gómez‐Ramírez, S., & García‐Erce, J. A. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.4666 · Cited by 67 · see citing works
Safety of intravenous iron in clinical practice: implications for anemia management protocols.
Aronoff, G. R. (2004) · PubMed · doi:10.1097/01.asn.0000143815.15433.87 · Cited by 66 · see citing works
Safety of Dextran in Relation to Other Colloids – Ten Years Experience with Hapten Inhibition
Ljungström, K.-G. (2009) · Infusionstherapie und Transfusionsmedizin / Infusion Therapy and Transfusion Medicine · doi:10.1159/000222845 · Cited by 64 · see citing works
EVOLUTION OF IV IRON COMPOUNDS OVER THE LAST CENTURY
Macdougall, I. C. (2009) · Journal of Renal Care · doi:10.1111/j.1755-6686.2009.00127.x · Cited by 60 · see citing works
McCarthy, J. T., Regnier, C. E., Loebertmann, C. L., & Bergstralh, E. J. (2000) · American Journal of Nephrology · doi:10.1159/000046199 · Cited by 56 · see citing works
Hédin, H., Richter, W., Meßmer, K., et al. (1980) · PubMed · Cited by 48 · see citing works
Funk, F., Long, G. J., Hautot, D., Büchi, R., Christl, I., & Weidler, P. G. (2001) · Hyperfine Interactions · doi:10.1023/a:1015552311359 · Cited by 44 · see citing works
An AutoAnalyzer Procedure for Serum Iron and Total Iron-Binding Capacity, with Use of Ferrozine
Yee, H. Y., & Zin, A. (1971) · Clinical Chemistry · doi:10.1093/clinchem/17.9.950 · Cited by 35 · see citing works
Hapten Inhibition of Passive Antidextran Dextran Anaphylaxis in Guinea Pigs
Richter, W. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000230575 · Cited by 35 · see citing works
Anaphylaxis with elevated serum tryptase after administration of intravenous ferumoxytol
Santosh, S., Podaralla, P., & Miller, B. W. (2010) · Clinical Kidney Journal · doi:10.1093/ndtplus/sfq084 · Cited by 29 · see citing works
Polymer characterization by liquid chromatography
Engelhardt, H. (1987) · Chromatographia · doi:10.1007/bf02316189 · Cited by 27 · see citing works
Anemia management in chronic kidney disease: Intravenous iron steps forward
Coyne, D. W., & Auerbach, M. (2010) · American Journal of Hematology · doi:10.1002/ajh.21682 · Cited by 23 · see citing works
Magnetostructural study of iron sucrose
Gutiérrez, L., Morales, M. P., & Lázaro, F. J. (2005) · Journal of Magnetism and Magnetic Materials · doi:10.1016/j.jmmm.2005.01.045 · Cited by 21 · see citing works
Auerbach, M., & Ballard, H. S. (2008) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2008.0045 · Cited by 19 · see citing works
Invited commentary: Pretreatment with dextran 1 makes dextran 40 therapy safer
Ljungström, K.-G. (2006) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2005.11.056 · Cited by 17 · see citing works
Jahn, M., Mrestani, Y., Langguth, P., & Neubert, R. H. H. (2007) · Electrophoresis · doi:10.1002/elps.200600559 · Cited by 11 · see citing works
Self-citationSome Observations on the Immunochemistry of Dextrans
Coulson, E. J., & Stevens, H. (1961) · The Journal of Immunology · doi:10.4049/jimmunol.86.3.241 · Cited by 10 · see citing works
OPTA-therapy with iron and erythropoiesis-stimulating agents in chronic kidney disease
Hörl, W. H., Macdougall, I. C., Rossert, J., et al. (2007) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfm014 · Cited by 10 · see citing works
Immune Complex Anaphylaxis Induced by Dextran and Its Elimination by Hapten Inhibition
Richter, A. W. (1986) · Springer eBooks · doi:10.1007/978-3-642-71316-3_29 · Cited by 7 · see citing works
Intravenous Iron in Cardiac Surgery
Múñoz, M., Leal-Noval, R., & García‐Erce, J. A. (2006) · Seminars in Hematology · doi:10.1053/j.seminhematol.2006.08.009 · Cited by 7 · see citing works
Richter, W. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000231091 · Cited by 6 · see citing works
Richter, W. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000230841 · Cited by 5 · see citing works
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Koskenkorva-Frank, T. S., Weiss, G., Koppenol, W. H., & Burckhardt, S. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.09.001 · Cited by 406 · see citing works
Intravenous iron therapy: how far have we come?
Cançado, R. D., & Muñoz, M. (2011) · Revista Brasileira de Hematologia e Hemoterapia · doi:10.5581/1516-8484.20110123 · Cited by 94 · see citing works
Self-citationIron deficiency anemia among women: An issue of health equity
Tang, G. H., & Sholzberg, M. (2024) · Blood Reviews · doi:10.1016/j.blre.2023.101159 · Cited by 60 · see citing works
Safety of intravenous iron use in chronic kidney disease
Kalra, P. A., & Bhandari, S. (2016) · Current Opinion in Nephrology and Hypertension · doi:10.1097/mnh.0000000000000263 · Cited by 50 · see citing works
Neiser, S., Koskenkorva, T., Schwarz, K., Wilhelm, M., & Burckhardt, S. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17071185 · Cited by 21 · see citing works
Burckhardt, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010122
- Authors
- Jahn, M. R., Andreasen, H. B., Fütterer, S., Nawroth, T., Schünemann, V., Kolb, U., Hofmeister, W., Muñoz, M., Bock, K., Meldal, M., & Langguth, P.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Pharmacosmos (Denmark) (DK)
- University of Kaiserslautern (DE)
- Carlsberg Laboratory (DK)
- Corresponding author
- Langguth, Peter
- Venue
- European Journal of Pharmaceutics and Biopharmaceutics
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 78
- Issue
- 3
- Pages
- 480-491
- ISSN
- 0939-6411 (ISSN-L)
- OpenAlex
- W2072414981
- Cited by
- 256
- References
- 46
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 11 · 2023: 22 · 2022: 22 · 2021: 15 · 2020: 15 · 2019: 20 · 2018: 17 · 2017: 25 · 2016: 19 · 2015: 14 · 2014: 15 · 2013: 18 · 2012: 12
- FWCI
- 10.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- iron isomaltoside 1000, iron deficiency anemia, iron dextran, sodium ferric gluconate, iron sucrose, iron carboxymaltose, ferumoxytol, labile iron, free iron, particle size, zeta potential, immunogenicity, parenteral iron
- MeSH terms
- Disaccharides, Drug Compounding, Ferric Compounds, Humans, Hydrolysis, Infusions, Intravenous, Molecular Weight, Particle Size, Vitamins, Molecular Structure, Drug Delivery Systems, Chemical Phenomena
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