Ferric cation
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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
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Hyperphosphatemia •••••••••••• Treatment of Iron deficiency anemia •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
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.
Hover over products below to view reaction partners
- 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
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. - Food Interactions
- Avoid milk and dairy products.
- Take with food. Take ferric cation with or just after meals.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Mixture Products
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. 2009-12-29 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. 2002-10-07 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 2334 more
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Iron Deficiency (ID) 1 somestatus stop reason just information to hide
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
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity)
- Specific Function
- double-stranded RNA binding
- 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
- 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 transport of all iron(3+)-hydroxamate siderophores such as ferrichrome, gallichrome, desferrioxamine, coprogen, aerobactin, shizokinen, rhodotorulic acid and the antibiotic albomycin.
- Specific Function
- Not Available
- 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
- 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 sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation
- Specific Function
- enzyme binding
- Gene Name
- TF
- Uniprot ID
- P02787
- Uniprot Name
- Serotransferrin
- Molecular Weight
- 77049.175 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
- Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets (By similarity). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887). In brain, plays a role in synaptic transmission and plasticity. Involved in the regulation of the serotonin neurotransmission, is required to localize to specific compartments within the synapse the serotonin receptor SLC6A4 and for an appropriate reuptake of serotonin. Controls excitatory synaptic strength by regulating GRIA2-containing AMPAR endocytosis, which affects AMPAR abundance and composition (By similarity). ITGAV:ITGB3 act as a receptor for CD40LG (PubMed:31331973). ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP (PubMed:10640428)
- Specific Function
- cell adhesion molecule binding
- 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
- 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 with almost all of the monoglucosylated glycoproteins that are synthesized in the ER (PubMed:7876246). Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export (PubMed:11149926). Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy (By similarity)
- Specific Function
- calcium ion binding
- 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