Identification
- Summary
Ferric cation is an iron supplement indicated in the treatment of iron deficiency anemia.
- Generic Name
- Ferric cation
- DrugBank Accession Number
- DB13949
- Background
Iron is a transition metal with a symbol Fe and atomic number 26. By mass, it is the most common element on Earth. Iron is an essential element involved in various metabolic processes, including oxygen transport, deoxyribonucleic acid (DNA) synthesis, and energy production in electron transport 1. Resulting from inadequate supply of iron to cells due to depletion of stores, iron deficiency is the most common nutritional deficiency worldwide, particularly affecting children, women of childbearing age, and pregnant women 8. Iron deficiency may be characterized without the development of anemia, and may result in functional impairments affecting cognitive development and immunity mechanisms, as well as infant or maternal mortality if it occurs during pregnancy 1. The main therapeutic preparation of iron is Ferrous sulfate, and iron-sucrose may also be given intravenously 7.
Iron exists in two oxidation states: the ferrous cation (Fe2+) and ferric cation (Fe3+). Non-haem iron in food is mainly in the ferric state, which is the insoluble form of iron, and must be reduced to the ferrous cation for absorption 7. Ferric citrate (tetraferric tricitrate decahydrate) is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Ferric cation (DB13949)
- Weight
- Average: 55.845
Monoisotopic: 55.934942133 - Chemical Formula
- Fe
- Synonyms
- FE (III) ION
- Fe(III)
- Ferric ion
- iron(3+)
Pharmacology
- Indication
For the control of serum phosphorus levels in patients with chronic kidney disease on dialysis, as ferric citrate.
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- Contraindications & Blackbox Warnings
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When Fe3+ is converted to soluble Fe2+, it primarily exists in the circulation in the complex forms bound to protein (hemoprotein) as heme compounds (hemoglobin or myoglobin), heme enzymes, or nonheme compounds (flavin-iron enzymes, transferring, and ferritin) 1. Once converted, Fe2+ serves to support various biological functions. Iron promotes the synthesis of oxygen transport proteins such as myoglobin and hemoglobin, and the formation of heme enzymes and other iron-containing enzymes involved in electron transfer and redox reactions 1. It also acts as a cofactor in many non-heme enzymes including hydroxylases and ribonucleotide reductase 8. Iron-containing proteins are responsible in mediating antioxidant actions, energy metabolism, oxygen sensing actions, and DNA replication and repair 8. Saturation of transferrin from high concentrations of unstable iron preparations may elevate the levels of weakly transferrin-bound Fe3+, which may induce oxidative stress by catalyzing lipid peroxidation and reactive oxygen species formation 5.
- Mechanism of action
Iron is incorporated into various proteins to serve biological functions as a structural component or cofactor. Once ferric or ferrous cation from intestinal enterocytes or reticuloendothelial macrophages is bound to circulating transferrin, iron-transferrin complex binds to the cell-surface transferrin receptor (TfR) 1, resulting in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of heme or iron-sulfur clusters, which are integral parts of several metalloproteins 1. Excess iron is stored and detoxified in cytosolic ferritin 1. Internalized Fe2+ exported across the basolateral membrane into the bloodstream via Fe+2 transporter ferroportin, which is coupled by reoxidation to Fe3+ via membrane-bound ferroxidase hephaestin or ceruloplasmin activity 1. Fe+3 is again scavenged by transferrin which maintains the ferric iron in a redox-inert state and delivers it into tissues 1.
Fe3+ participates in the autoxidation reaction, where it can be chelated by DNA. It mainly binds to the backbone phosphate group, whereas at higher metal ion content, the cation binds to both guanine N-7 atom and the backbone phosphate group 2.
Target Actions Organism ATransferrin receptor protein 1 agonistHumans UIron(3+)-hydroxamate-binding protein FhuD binderEscherichia coli (strain K12) - Absorption
Iron absorption and systemic iron homeostasis are regulated by hepcidin, which is a peptide hormone that also regulates the activity of the iron-efflux protein, ferroportin-1 1. Iron is mostly absorbed in the duodenum and upper jejunum 9. Fe3+ displays low solubility at the neutral pH of the intestine and is mainly be converted to ferrous iron (Fe2+) by ferric reductases 7, as ferric salts are only half as well absorbed as ferrous salts 9. Once converted in the intestinal lumen, Fe+2 is transported across the apical membrane of enterocytes 1. The absorption rate of non-haem iron is 2-20% 1. Stored iron may be liberated via ferroportin-mediated efflux, which is coupled by reoxidation of Fe2+ to Fe3+ by ceruloplasmin in the serum or hephaestin in the enterocyte membrane 5. Fe3+ subsequently binds to transferrin, which keeps ferric cation in a redox-inert state and delivers it into tissues 1.
It is proposed that there may be separate cellular uptake pathways for ferrous iron and ferric iron. While ferrous iron is primarily carried by divalent metal transporter-1 (DMAT-1), cellular uptake of ferric iron is predominantly mediated by beta-3 integrin and mobilferrin, which is also referred to as calreticulin in some sources as a homologue 4. However, the most dominant pathway in humans is unclear 4.
- Volume of distribution
Less than 65% of iron is stored in the liver, spleen, and bone marrow, mainly as ferritin and haemosiderin 7. The pharmacokinetic properties of ferric compounds vary.
- Protein binding
Fe3+ is converted to Fe2+, which is bound and transported in the body via circulating transferrin. In pathogenic Neisseria, ferric iron-binding protein serves as the main periplasmic-protein for ferric iron that has equivalence to human transferrin 3. Once in the cytosol, ferric iron is stored in ferritin where it is associated with hydroxide and phosphate anions 6.
- Metabolism
Ferric cation is converted to ferrous iron by duodenal cytochrome B reductase. Ferritin may also convert ferric to ferrous iron 6.
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- Route of elimination
Iron is predominantly conserved in the body with no physiologic mechanism for excretion of excess iron from the body, other than blood loss 1. The pharmacokinetic properties of ferric compounds vary.
- Half-life
The pharmacokinetic properties of ferric compounds vary.
- Clearance
The rate of iron loss is approximately 1 mg/day 1. The pharmacokinetic properties of ferric compounds vary.
- Adverse Effects
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The LD50 of ferric compounds vary. High concentrations of ferric iron from unstable and oversaturation of ferritin may lead to adverse events such as hypotension, nausea, vomiting, abdominal and lower back pain, peripheral edema and a metallic taste 5.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAlendronic acid Ferric cation can cause a decrease in the absorption of Alendronic acid resulting in a reduced serum concentration and potentially a decrease in efficacy. Almasilate Almasilate can cause a decrease in the absorption of Ferric cation resulting in a reduced serum concentration and potentially a decrease in efficacy. Aluminium phosphate Aluminium phosphate can cause a decrease in the absorption of Ferric cation resulting in a reduced serum concentration and potentially a decrease in efficacy. Aluminum hydroxide Aluminum hydroxide can cause a decrease in the absorption of Ferric cation resulting in a reduced serum concentration and potentially a decrease in efficacy. Asenapine Asenapine can cause a decrease in the absorption of Ferric cation resulting in a reduced serum concentration and potentially a decrease in efficacy. Cabotegravir The serum concentration of Cabotegravir can be decreased when it is combined with Ferric cation. Calcium carbonate Calcium carbonate can cause a decrease in the absorption of Ferric cation resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium Phosphate Ferric cation can cause a decrease in the absorption of Calcium Phosphate resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium phosphate dihydrate Ferric cation can cause a decrease in the absorption of Calcium phosphate dihydrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Carbidopa Ferric cation can cause a decrease in the absorption of Carbidopa resulting in a reduced serum concentration and potentially a decrease in efficacy. 
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- Avoid milk and dairy products.
- Take with food. Take ferric cation with or just after meals.
Products
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Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image FERIMAX FORT ÇİĞNEME TABLETİ, 30 ADET Ferric cation (100 mg) + Icosapent (0.35 mg) Tablet, chewable Oral BİLİM İLAÇ SAN. VE TİC. A.Ş. 2020-08-14 Not applicable Turkey 
MALTOFER FOL 100 MG/0.35 MG TABLET, 30 ADET Ferric cation (100 mg) + Folic acid (0.35 mg) Tablet Oral ABDİ İBRAHİM İLAÇ SAN. VE TİC. A.Ş. 2020-08-14 Not applicable Turkey
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 91O4LML611
- CAS number
- 20074-52-6
- InChI Key
- VTLYFUHAOXGGBS-UHFFFAOYSA-N
- InChI
- InChI=1S/Fe/q+3
- IUPAC Name
- iron(3+) ion
- SMILES
- [Fe+3]
References
- General References
- Abbaspour N, Hurrell R, Kelishadi R: Review on iron and its importance for human health. J Res Med Sci. 2014 Feb;19(2):164-74. [Article]
- Ouameur AA, Arakawa H, Ahmad R, Naoui M, Tajmir-Riahi HA: A Comparative study of Fe(II) and Fe(III) interactions with DNA duplex: major and minor grooves bindings. DNA Cell Biol. 2005 Jun;24(6):394-401. doi: 10.1089/dna.2005.24.394. [Article]
- Chen CY, Berish SA, Morse SA, Mietzner TA: The ferric iron-binding protein of pathogenic Neisseria spp. functions as a periplasmic transport protein in iron acquisition from human transferrin. Mol Microbiol. 1993 Oct;10(2):311-8. doi: 10.1111/j.1365-2958.1993.tb01957.x. [Article]
- Conrad ME, Umbreit JN, Moore EG, Hainsworth LN, Porubcin M, Simovich MJ, Nakada MT, Dolan K, Garrick MD: Separate pathways for cellular uptake of ferric and ferrous iron. Am J Physiol Gastrointest Liver Physiol. 2000 Oct;279(4):G767-74. doi: 10.1152/ajpgi.2000.279.4.G767. [Article]
- Geisser P, Burckhardt S: The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011 Jan 4;3(1):12-33. doi: 10.3390/pharmaceutics3010012. [Article]
- Waldvogel-Abramowski S, Waeber G, Gassner C, Buser A, Frey BM, Favrat B, Tissot JD: Physiology of iron metabolism. Transfus Med Hemother. 2014 Jun;41(3):213-21. doi: 10.1159/000362888. Epub 2014 May 12. [Article]
- 25. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 310-312). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
- Iron [Link]
- InChem: Iron [Link]
- TITCK: Ferimax (Ferric Cation) Oral Drops [Link]
- External Links
- PDB Entries
- 1a8e / 1a8f / 1ahj / 1aor / 1ar5 / 1aui / 1avm / 1b06 / 1b0l / 1b13 … show 2159 more
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count Not Available Completed Not Available Iron Deficiency (ID) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Oral 100 mg/5ml Solution / drops Oral 50 mg/ml Tablet, chewable Oral Solution Oral Tablet Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8846976 No 2014-09-30 2024-02-18 US 
US8093423 No 2012-01-10 2026-04-21 US US5753706 No 1998-05-19 2017-02-03 US US8338642 No 2012-12-25 2024-02-18 US US9050316 No 2015-06-09 2024-02-18 US US8901349 No 2014-12-02 2024-02-18 US US8754258 No 2014-06-17 2024-02-18 US US7767851 No 2010-08-03 2024-02-18 US US8754257 No 2014-06-17 2024-02-18 US US8609896 No 2013-12-17 2024-02-18 US US8299298 No 2012-10-30 2024-02-18 US US9387191 No 2016-07-12 2030-07-21 US US9328133 No 2016-05-03 2024-02-18 US US9757416 No 2017-09-12 2024-02-18 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 3000 MSDS boiling point (°C) 1535 MSDS water solubility Insoluble MSDS - Predicted Properties
Property Value Source logP -0.77 Chemaxon pKa (Strongest Acidic) 4.58 Chemaxon Physiological Charge 3 Chemaxon Hydrogen Acceptor Count 0 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 0 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 0 m3·mol-1 Chemaxon Polarizability 1.78 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Virus receptor activity
- Specific Function
- Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferri...
- Gene Name
- TFRC
- Uniprot ID
- P02786
- Uniprot Name
- Transferrin receptor protein 1
- Molecular Weight
- 84870.665 Da
References
- Hemadi M, Ha-Duong NT, El Hage Chahine JM: The mechanism of iron release from the transferrin-receptor 1 adduct. J Mol Biol. 2006 May 12;358(4):1125-36. Epub 2006 Mar 13. [Article]
- Geisser P, Burckhardt S: The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011 Jan 4;3(1):12-33. doi: 10.3390/pharmaceutics3010012. [Article]
- Waldvogel-Abramowski S, Waeber G, Gassner C, Buser A, Frey BM, Favrat B, Tissot JD: Physiology of iron metabolism. Transfus Med Hemother. 2014 Jun;41(3):213-21. doi: 10.1159/000362888. Epub 2014 May 12. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Part of the ABC transporter complex FhuCDB involved in iron(3+)-hydroxamate import. Binds the iron(3+)-hydroxamate complex and transfers it to the membrane-bound permease. Required for the transpor...
- Gene Name
- fhuD
- Uniprot ID
- P07822
- Uniprot Name
- Iron(3+)-hydroxamate-binding protein FhuD
- Molecular Weight
- 32997.965 Da
References
- Clarke TE, Rohrbach MR, Tari LW, Vogel HJ, Koster W: Ferric hydroxamate binding protein FhuD from Escherichia coli: mutants in conserved and non-conserved regions. Biometals. 2002 Jun;15(2):121-31. [Article]
- Koster W, Braun V: Iron (III) hydroxamate transport into Escherichia coli. Substrate binding to the periplasmic FhuD protein. J Biol Chem. 1990 Dec 15;265(35):21407-10. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Transferrin receptor binding
- Specific Function
- Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from si...
- Gene Name
- TF
- Uniprot ID
- P02787
- Uniprot Name
- Serotransferrin
- Molecular Weight
- 77063.195 Da
References
- Abbaspour N, Hurrell R, Kelishadi R: Review on iron and its importance for human health. J Res Med Sci. 2014 Feb;19(2):164-74. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Virus receptor activity
- Specific Function
- Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Wil...
- Gene Name
- ITGB3
- Uniprot ID
- P05106
- Uniprot Name
- Integrin beta-3
- Molecular Weight
- 87056.975 Da
References
- Conrad ME, Umbreit JN, Moore EG, Hainsworth LN, Porubcin M, Simovich MJ, Nakada MT, Dolan K, Garrick MD: Separate pathways for cellular uptake of ferric and ferrous iron. Am J Physiol Gastrointest Liver Physiol. 2000 Oct;279(4):G767-74. doi: 10.1152/ajpgi.2000.279.4.G767. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Zinc ion binding
- Specific Function
- Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently wit...
- Gene Name
- CALR
- Uniprot ID
- P27797
- Uniprot Name
- Calreticulin
- Molecular Weight
- 48141.2 Da
References
- Conrad ME, Umbreit JN, Moore EG, Hainsworth LN, Porubcin M, Simovich MJ, Nakada MT, Dolan K, Garrick MD: Separate pathways for cellular uptake of ferric and ferrous iron. Am J Physiol Gastrointest Liver Physiol. 2000 Oct;279(4):G767-74. doi: 10.1152/ajpgi.2000.279.4.G767. [Article]
Drug created at January 12, 2018 17:15 / Updated at February 03, 2022 06:26