Chromium nicotinate
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Identification
- Summary
Chromium nicotinate is a medication used to treat chromium deficiencies and associated symptoms and also in total parenteral nutrition.
- Generic Name
- Chromium nicotinate
- DrugBank Accession Number
- DB14529
- Background
Not Available
- Type
- Small Molecule
- Groups
- Approved, Experimental
- Structure
- Weight
- Average: 418.305
Monoisotopic: 418.013116 - Chemical Formula
- C18H12CrN3O6
- Synonyms
- Chromium(III) nicotinate
Pharmacology
- Indication
Indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN), to maintain chromium serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms Label.
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- Pharmacodynamics
Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity 2. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency Label.
- Mechanism of action
Chromium is an essential nutrient involved in the metabolism of glucose, insulin and blood lipids. Its role in potentiating insulin signalling cascades has been implicated in several studies. Chromium upregulates insulin-stimulated insulin signal transduction via affecting effector molecules downstream of the insulin receptor (IR). IR-mediated signalling pathway involves phoshorylation of multiple intracellular domains and protein kinases, and downstream effector molecules 3. Upon activation by ligands, intracellular β-subunit of IR autophosphorylates and activates tyrosine kinase domain of the IR, followed by activation and phosphorylation of regulatory proteins and downstream signalling effectors including phosphatidylinositol 2-kinase (PI3K). PI3K activates further downstream reaction cascades to activate protein kinase B (Akt) to ultimately promote translocation of glucose transporter-4 (Glut4)-vesicles from the cytoplasm to the cell surface and regulate glucose uptake 3. Chromium enhances the kinase activity of insulin receptor β and increases the activity of downstream effectors, pI3-kinase and Akt.
Under insulin-resistant conditions, chromium also promotes GLUT-4 transporter translocation that is independent of activity of IR, IRS-1, PI3-kinase, or Akt; chromium mediates cholesterol efflux from the membranes via increasing fluidity of the membrane by decreasing the membrane cholesterol and upregulation of sterol regulatory element-binding protein 3. As a result, intracellular GLUT-4 transporters are stimulated to translocate from intracellular to the plasma membrane, leading to enhanced glucose uptake in muscle cells 8. Chromium attenuates the activity of PTP-1B in vitro, which is a negative regulator of insulin signaling. It also alleviates ER stress that is observed to be elevated the suppression of insulin signaling. ER stress is thought to activate c-Jun N-terminal kinase (JNK), which subsequently induces serine phosphorylation of IRS and aberration of insulin signalling 3. Transient upregulation of AMPK by chromium also leads to increased glucose uptake 3.
Target Actions Organism UCytochrome b5 Not Available Humans - Absorption
Chromium compounds are both absorbed by the lung and the gastrointestinal tract. Oral absorption of chromium compounds in humans can range between 0.5% and 10%, with the hexavalent (VI) chromium more easily absorbed than the trivalent (III) form 5. Absorption of chromium from the intestinal tract is low, ranging from less than 0.4% to 2.5% of the amount consumed 7. Vitamin C and the vitamin B niacin is reported to enhance chromium absorption 7.
Most hexavalent Cr (VI) undergoes partial intragastric reduction to Cr (III) upon absorption, which is an action mainly mediated by sulfhydryl groups of amino acids 5. Cr (VI) readily penetrates cell membranes and chromium can be found in both erythrocytes and plasma after gastrointestinal absorption of Cr (IV). In comparison, the presence of chromium is limited to the plasma as Cr (III) displays poor cell membrane penetration 5. Once transported through the cell membrane, Cr (VI) is rapidly reduced to Cr (III), which subsequently binds to macromolecules or conjugate with proteins. Cr (III) may be bound to transferrin or other plasma proteins, or as complexes, such as glucose tolerance factor (GTF).
- Volume of distribution
Absorbed chromium is distributed to all tissues of the body and its distribution in the body depends on the species, age, and chemical form 8. Circulating Cr (III) following oral or parenteral administration of different compounds can be taken up by tissues and accumulates in the liver, kidney, spleen, soft tissue, and bone 7.
- Protein binding
In the blood, 95% of chromium (III) is bound to large molecular mass proteins, such as transferrin, while a small proportion associates with low molecular mass oligopeptides 6. Serum chromium is bound to transferrin in the beta globulin fraction Label.
- Metabolism
The metabolism of Cr (VI) involves reduction by small molecules and enzyme systems to generate Cr (III) and reactive intermediates. During this process, free radicals can be generated, which is thought to induce damage of cellular components and cause toxicity of chromium 6. The metabolites bind to cellular constituents 5.
- Route of elimination
Absorbed chromium is excreted mainly in the urine, accounting for 80% of total excretion of chromium; small amounts are lost in hair, perspiration and bile 5. Chromium is excreted primarily in the urine by glomerular filtration or bound to a low molecular-weight organic transporter 8.
- Half-life
The elimination half-life of hexavalent chromium is 15 to 41 hours 5.
- Clearance
Excretion of chromium is via the kidneys ranges from 3 to 50 μg/day Label. The 24-hour urinary excretion rates for normal human subjects are reported to be 0.22 μg/day 8.
- Adverse Effects
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- Toxicity
Oral LD50 for Cr (VI) is 135 - 175 mg/kg in mouse and 46 - 113 mg/kg in rat 5. Oral LD50 for Cr (III) in rat is >2000 mg/kg 5. LD50 of chromium (III) oxide in rats is reported to be > 5g/kg 6. Other LD50 values reported for rats include: 3.5 g/kg (CI 3.19-3.79 g/kg) for chromium sulphate; 11.3 g/kg for chromium (III) acetate; 3.3 g/kg for chromium nitrate; and 1.5 g/kg for chromium nitrate nonahydrate 6.
Acute overdose of chromium is rare and seriously detrimental effects of hexavalent chromium are primarily the result of chronic low-level exposure 5. In case of overdose with minimal toxicity following acute ingestion, treatment should be symptomatic and supportive 5. There is no known antidote for chromium toxicity.
Hexavalent chromium is a Class A carcinogen by the inhalation route of exposure and Class D by the oral route 5. The oral lethal dose in humans has been estimated to be 1-3 g of Cr (VI); oral toxicity most likely involves gastrointestinal bleeding rather than systemic toxicity 5. Chronic exposure may cause damage to the following organs: kidneys, lungs, liver, upper respiratory tract MSDS. Soluble chromium VI compounds are human carcinogens. Hexavalent chromium compounds were mutagenic in bacteria assays and caused chromosome aberrations in mammalian cells. There have been associations of increased frequencies of chromosome aberrations in lymphocytes from chromate production workers 4. In human cells in vitro, Cr (VI) caused chromosomal aberrations, sister chromatid exchanges and oxidative DNA damage 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 softwareAbacavir Abacavir may decrease the excretion rate of Chromium nicotinate which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Chromium nicotinate which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Chromium nicotinate which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Chromium nicotinate which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Chromium nicotinate which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Administer vitamin supplements. Foods or supplements containing niacin (Vitamin B3) may improve the absorption of chromium.
- Take with foods containing vitamin C. Foods rich in vitamin C increase the absorption of chromium.
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.
- Active Moieties
Name Kind UNII CAS InChI Key Niacin unknown 2679MF687A 59-67-6 PVNIIMVLHYAWGP-UHFFFAOYSA-N - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image DAILY-ONE 45 FILM TABLET Chromium nicotinate (0.13 mg) + Ascorbic acid (90 mg) + Beta carotene (2000 IU) + Biotin (0.06 mg) + Calcium phosphate, tribasic (100 mg) + Calcium phosphate, tribasic (50 mg) + Choline bitartrate (3.9 mg) + Cupric sulfate (2 mg) + Cyanocobalamin (0.015 mg) + Egg phospholipids (23 mg) + Ferrous fumarate (18 mg) + Folic acid (0.4 mg) + Inositol (3.9 mg) + Magnesium oxide (40 mg) + Manganese sulfate (3.5 mg) + Niacin (20 mg) + Pantothenic acid (20 mg) + Potassium Iodide (0.15 mg) + Potassium citrate (18 mg) + Pyridoxine hydrochloride (12 mg) + Riboflavin (10.2 mg) + Sodium selenite (0.07 mg) + Sodium molybdate (0.05 mg) + Thiamine hydrochloride (9 mg) + Vitamin A acetate (8000 IU) + Vitamin D (400 IU) + Vitamin E (60 IU) + Zinc gluconate (15 mg) Tablet, film coated FERROSAN SAĞLIK ÜRÜN VE HİZMETLERİ A.Ş. 1996-06-17 Not applicable Turkey Omega-3 Rx Complete Chromium nicotinate (.12 mg/1) + Ascorbic acid (60 mg/1) + Biotin (.075 mg/1) + Calcium (210 mg/1) + Copper (2 mg/1) + Cyanocobalamin (.018 mg/1) + Folic acid (.4 mg/1) + Lycopene (.3 mg/1) + Magnesium (140 mg/1) + Magnesium oxide (140 mg/1) + Nicotinamide (18 mg/1) + Omega-3-acid ethyl esters (1 g/1) + Pantothenic acid (.016 mg/1) + Phylloquinone (.020 mg/1) + Riboflavin (1.7 mg/1) + Selenium (.11 mg/1) + Thiamine chloride (1.35 mg/1) + Vitamin A (3500 [iU]/1) + Vitamin D (700 [iU]/1) + Vitamin E (22.5 [iU]/1) + Zinc oxide (15 mg/1) Kit Oral Tmig, Inc. 2015-09-01 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image DermaNIC Chromium nicotinate (0.57 mg/1) + Acetylcysteine zinc (69.5 mg/1) + Ferrous cysteine glycinate (1.5 mg/1) + Folic acid (500 ug/1) + Hydroxocobalamin (15 ug/1) + Inositol nicotinate (328 mg/1) + Niacin (1.5 mg/1) + Nicotinamide (498 mg/1) Tablet Oral Allegis Pharmaceuticals, LLC 2014-02-03 2016-12-01 US Finazol Chromium nicotinate (37.5 ug/1) + Ascorbic acid (200 mg/1) + Biotin (100 ug/1) + Boron (25 ug/1) + Calcium carbonate (100 mg/1) + Cholecalciferol (10 ug/1) + Cupric oxide (1 mg/1) + DL-alpha tocopheryl acetate (45 mg/1) + Ferrous fumarate (18 mg/1) + Levomefolate calcium (1000 ug/1) + Magnesium oxide (50 mg/1) + Manganese sulfate (0.75 mg/1) + Mecobalamin (26 ug/1) + Molybdenum (25 ug/1) + Nicotinamide (22.5 mg/1) + Pantothenic acid (15 mg/1) + Potassium Iodide (25 ug/1) + Potassium chloride (24.5 mg/1) + Pyridoxine hydrochloride (6 mg/1) + Riboflavin (3.35 mg/1) + Selenium (30 ug/1) + Thiamine mononitrate (3.25 mg/1) + Vitamin A acetate (1500 ug/1) + Zinc citrate (30 mg/1) Tablet Oral PureTek Corporation 2024-10-11 Not applicable US Foliflex Chromium nicotinate (37.5 ug/1) + Ascorbic acid (250 mg/1) + Biotin (100 ug/1) + Boron (25 ug/1) + Calcium carbonate (75 mg/1) + Cholecalciferol (13.75 ug/1) + Cupric oxide (1 mg/1) + Cyanocobalamin (13 ug/1) + DL-alpha tocopheryl acetate (45 mg/1) + Ferrous fumarate (9 mg/1) + Folic acid (500 ug/1) + Magnesium oxide (37.5 mg/1) + Manganese sulfate (0.75 mg/1) + Molybdenum (25 ug/1) + Nicotinamide (22.5 mg/1) + Pantothenic acid (15 mg/1) + Potassium Iodide (25 ug/1) + Potassium chloride (24.5 mg/1) + Pyridoxine hydrochloride (6 mg/1) + Riboflavin (3.35 mg/1) + Selenium (30 ug/1) + Thiamine mononitrate (3.25 mg/1) + Vitamin A acetate (1500 ug/1) + Zinc oxide (15 mg/1) Tablet Oral PureTek Corporation 2021-10-25 Not applicable US Folitin-Z Chromium nicotinate (37.5 ug/1) + Ascorbic acid (250 mg/1) + Biotin (100 ug/1) + Boron (25 ug/1) + Calcium carbonate (75 mg/1) + Cholecalciferol (13.75 ug/1) + Cupric oxide (1 mg/1) + Cyanocobalamin (13 ug/1) + DL-alpha tocopheryl acetate (45 mg/1) + Ferrous fumarate (9 mg/1) + Folic acid (500 ug/1) + Magnesium oxide (37.5 mg/1) + Manganese sulfate (0.75 mg/1) + Molybdenum (25 ug/1) + Nicotinamide (22.5 mg/1) + Pantothenic acid (15 mg/1) + Potassium Iodide (25 ug/1) + Potassium chloride (24.5 mg/1) + Pyridoxine hydrochloride (6 mg/1) + Riboflavin (3.35 mg/1) + Selenium (30 ug/1) + Thiamine mononitrate (3.25 mg/1) + Vitamin A acetate (1500 ug/1) + Zinc oxide (15 mg/1) Tablet Oral PureTek Corporation 2021-02-11 Not applicable US Multitam Chromium nicotinate (35 ug/1) + Ascorbic acid (120 mg/1) + Calcium carbonate (200 mg/1) + Cholecalciferol (20 ug/1) + Cyanocobalamin (8 ug/1) + DL-alpha tocopheryl acetate (30 mg/1) + Folic acid (1000 ug/1) + Magnesium oxide (200 mg/1) + Manganese sulfate (2.3 mg/1) + Molybdenum (45 ug/1) + Nicotinamide (20 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (3.4 mg/1) + Selenium (55 ug/1) + Thiamine mononitrate (3 mg/1) + Vitamin A acetate (1500 ug/1) + Zinc oxide (25 mg/1) Tablet Oral PureTek Corporation 2022-01-17 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyridinecarboxylic acids. These are compounds containing a pyridine ring bearing a carboxylic acid group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Pyridinecarboxylic acids and derivatives
- Direct Parent
- Pyridinecarboxylic acids
- Alternative Parents
- Heteroaromatic compounds / Carboxylic acid salts / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic zwitterions / Organic oxides show 2 more
- Substituents
- Aromatic heteromonocyclic compound / Azacycle / Carboxylic acid / Carboxylic acid derivative / Carboxylic acid salt / Heteroaromatic compound / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Organic chromium salt / Organic nitrogen compound show 9 more
- Molecular Framework
- Not Available
- External Descriptors
- chromium coordination entity (CHEBI:50368)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- A150AY412V
- CAS number
- 64452-96-6
- InChI Key
- MSPQQAUTCRWLGR-UHFFFAOYSA-K
- InChI
- InChI=1S/3C6H5NO2.Cr/c3*8-6(9)5-2-1-3-7-4-5;/h3*1-4H,(H,8,9);/q;;;+3/p-3
- IUPAC Name
- chromium(3+) tris(pyridine-3-carboxylate)
- SMILES
- [Cr+3].[O-]C(=O)C1=CN=CC=C1.[O-]C(=O)C1=CN=CC=C1.[O-]C(=O)C1=CN=CC=C1
References
- General References
- Wallach S: Clinical and biochemical aspects of chromium deficiency. J Am Coll Nutr. 1985;4(1):107-20. [Article]
- Anderson RA: Chromium in the prevention and control of diabetes. Diabetes Metab. 2000 Feb;26(1):22-7. [Article]
- Hua Y, Clark S, Ren J, Sreejayan N: Molecular mechanisms of chromium in alleviating insulin resistance. J Nutr Biochem. 2012 Apr;23(4):313-9. doi: 10.1016/j.jnutbio.2011.11.001. [Article]
- CHROMIUM, ELEMENTAL - National Library of Medicine HSDB ... - Toxnet - NIH [Link]
- CHROMIUM COMPOUNDS - National Library of Medicine HSDB ... - Toxnet - NIH [Link]
- Chromium Toxicological Overview - Health Protection Agency - Gov.uk [Link]
- Dietary Supplement Fact Sheet: Chromium [Link]
- Dailymed Label: DIVISTA - chromium picolinate capsule [Link]
- External Links
- ChemSpider
- 8085563
- ChEBI
- 50368
- Wikipedia
- Chromium(III)_nicotinate
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 Unknown Status Treatment Alcohol Dependency 1 somestatus stop reason just information to hide 2 Completed Prevention Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide 2, 3 Completed Treatment Substance Abuse / Substance Dependence 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Tablet, coated Oral Tablet Oral Kit Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0286 mg/mL ALOGPS logP 2.08 ALOGPS logP -0.17 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 2.79 Chemaxon pKa (Strongest Basic) 4.19 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 53.02 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 41.99 m3·mol-1 Chemaxon Polarizability 10.86 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No 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
- Unknown
- General Function
- Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases
- Specific Function
- cytochrome-c oxidase activity
- Gene Name
- CYB5A
- Uniprot ID
- P00167
- Uniprot Name
- Cytochrome b5
- Molecular Weight
- 15329.985 Da
References
- Jannetto PJ, Antholine WE, Myers CR: Cytochrome b(5) plays a key role in human microsomal chromium(VI) reduction. Toxicology. 2001 Feb 28;159(3):119-33. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Moshtaghie AA, Ani M, Bazrafshan MR: Comparative binding study of aluminum and chromium to human transferrin. Effect of iron. Biol Trace Elem Res. 1992 Jan-Mar;32:39-46. [Article]
Drug created at July 12, 2018 19:29 / Updated at January 08, 2021 01:07