Identification

Name
Magnesium gluconate
Accession Number
DB13749
Type
Small Molecule
Groups
Approved, Investigational
Description

Magnesium gluconate is a magnesium salt of gluconate. It demonstrates the highest oral bioavailability of magnesium salts [14] and is used as a mineral supplement. Magnesium is ubiquitous in the human body, and is naturally present in many foods, added to other food products, available as a dietary supplement and used as an ingredient in some medicines (such as antacids and laxatives) [9].

Although magnesium is available in the form of sulphates, lactate, hydroxide, oxide and chloride, only magnesium gluconate is recommended for magnesium supplementation as it appears to be better absorbed and causes less diarrha [6].

This drug has been studied in the prevention of pregnancy-induced hypertension, and has displayed promising results [1]. In addition, it has been studied for its effects on premature uterine contractions [2].

Structure
Thumb
Synonyms
  • Magnesium (as gluconate)
  • Magnesium D-gluconate (1:2) dihydrate
  • Magnesium D-gluconate (1:2) hydrate
  • Magnesium gluconate,dihydrate
  • Magnesium gluconicum
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
K-medMagnesium gluconate (341 mg) + Potassium Chloride (600 mg)TabletOralLaboratoire Riva Inc1988-12-312008-07-30Canada
Categories
UNII
T42NAD2KHC
CAS number
59625-89-7
Weight
Average: 450.629
Monoisotopic: 450.10712646
Chemical Formula
C12H26MgO16
InChI Key
HJWFTNWQKDPLAS-SYAJEJNSSA-L
InChI
InChI=1S/2C6H12O7.Mg.2H2O/c2*7-1-2(8)3(9)4(10)5(11)6(12)13;;;/h2*2-5,7-11H,1H2,(H,12,13);;2*1H2/q;;+2;;/p-2/t2*2-,3-,4+,5-;;;/m11.../s1
IUPAC Name
magnesium(2+) ion bis((2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoate) dihydrate
SMILES
O.O.[Mg++].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O

Pharmacology

Indication

Magnesium gluconate is a mineral supplement which is used to prevent and treat low levels of magnesium. Magnesium is very important for the normal physiologic functioning of cells, nerves, muscles, bones, and the heart. Generally, a well-balanced diet provides the necessary amounts of magnesium for homeostasis. However, certain conditions causing chronic magnesium deficiency may decrease levels of magnesium. These conditions include treatment with diuretics, a poor diet, alcoholism, or other medical conditions (e.g., severe diarrhea/vomiting, stomach/intestinal absorption problems, poorly controlled diabetes) [8].

Pharmacodynamics

Magnesium is a cofactor in over 300 enzyme systems that regulate a variety of biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. Magnesium is necessary for energy production, oxidative phosphorylation, and glycolysis [9].

Mechanism of action

Replaces deficient circulating levels of magnesium [10].

By competing with calcium for membrane binding sites and by stimulating calcium sequestration by sarcoplasmic reticulum, magnesium helps in the maintenance of a low resting intracellular free calcium ion concentration, which is essential in various cellular functions. The electrical properties of membranes and their permeability characteristics are also affected by magnesium [6].

Magnesium is essential to many enzymatic reactions in the body, serving as a cofactor in protein synthesis and in carbohydrate metabolism [12].

Magnesium contributes to the structural development of bone and is also essential in the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays an important role in the active transport of calcium and potassium ions across cell membranes, a process which is important to nerve impulse conduction, muscle contraction, and normal heart rhythm [9].

In addition to the above, magnesium is an essential mineral required for the regulation of body temperature, nucleic acid and protein synthesis, and in preserving nerve and muscle cell electrical potentials. Magnesium supplementation during pregnancy may help to reduce fetal growth restriction and pre-eclampsia, as well to increase birth weight [4].

Absorption

A high-fat diet may decrease the amount of magnesium absorbed in the diet. Over-cooking food also may decrease the amount of magnesium absorbed from dietary sources [10].

About 1/3 of magnesium is absorbed from the small intestine. The fraction of magnesium absorbed is inversely proportional to amount ingested [12].

Oral absorption is estimated to be 15% to 30% [11].

Volume of distribution

About 60% of the magnesium is present in bone, of which 30% is exchangeable and functions as a reservoir to stabilize the serum concentration. About 20% is found in skeletal muscle, 19% in other soft tissues and less than 1% in the extracellular fluid. Skeletal muscle and liver contain between 7–9 mmol/Kg wet tissue; between 20–30% of this is readily exchangeable. In healthy adults, the total serum magnesium is in the range of 0.70 and 1.10 mmol/L. Approximately 20% of this is protein bound, 65% is ionized and the rest is combined with various anions such as phosphate and citrate [6].

Protein binding

Approximately 25-30% [12].

Of the protein bound fraction, 60–70% is associated with albumin and the rest is bound to other globulins [6].

Metabolism
Not Available
Route of elimination

Oral: Via urine (absorbed fraction); feces (unabsorbed fraction) [12].

Phosphate depletion is associated with a significant increase in urinary magnesium excretion and may lead to hypomagnesemia. Hypercalcemia is associated with an increased urinary excretion of magnesium. The increase in magnesium excretion in hypercalcemia is greater than the increase in calcium excretion and is due to decreased reabsorption in the loop of Henle. Hypercalcaemia leads to a reduction in isotonic reabsorption in the proximal renal tubule causing greater delivery of sodium, water, calcium and magnesium to the loop of Henle. As a result of this increased flow to thick ascending loop of henle, calcium and magnesium transport may be inhibited. In addition, the high peritubular concentration of calcium directly inhibits the transport of both ions in this segment [6].

Osmotic diuretics such as mannitol and glucose cause a marked increase in magnesium excretion. Loop diuretics induce hypermagnesuria, and the increase in magnesium excretion is greater than that of sodium or calcium suggesting that loop diuretics may directly inhibit magnesium transport [6].

Half life
Not Available
Clearance

The kidney plays a major role in magnesium homeostasis and the maintenance of plasma magnesium concentration. Under normal circumstances, when 80% of the total plasma magnesium is ultrafiltrable, 84 mmol of magnesium is filtered daily and 95% of this amount it reabsorbed leaving about 3–5 mmol to be excreted in the urine [6].

Toxicity

Oral LD50 is 9100 mg/kg in the rat [15].

Excess magnesium from dietary sources does not pose a health risk in healthy individuals because the kidneys eliminate excess amounts of magnesium in the urine. On the other hand, high doses of magnesium from dietary supplements or medications often result in diarrhea that can be combined with nausea and abdominal cramping. Forms of magnesium most commonly reported to cause diarrhea include magnesium carbonate, chloride, gluconate, and oxide. Diarrheal and laxative effects of magnesium salts are due to the osmotic activity of unabsorbed salts in the intestine and colon and the stimulation of gastric motility [12].

Hypermagnesaemia after oral ingestion is uncommon except in patients with renal impairment. Signs and symptoms of hypermagnesemia may include respiratory depression, loss of deep tendon reflexes due to neuromuscular blockade, nausea, vomiting, flushing, hypotension, drowsiness, bradycardia and muscle weakness.

Very high doses of magnesium-containing laxatives and antacids (normally providing more than 5,000 mg/day magnesium) have been associated with the occurrence of magnesium toxicity, including fatal hypermagnesemia in a 28-month-old boy as well as an elderly man. Symptoms of magnesium toxicity, normally presenting at concentrations of 1.74–2.61 mmol/L, may include hypotension, nausea, vomiting, facial flushing, retention of urine, ileus, depression, and lethargy before progressing to muscle weakness, difficulty breathing, extreme hypotension, irregular heartbeat, and cardiac arrest. The risk of magnesium toxicity increases with compromised renal function or kidney failure because the ability to remove excess magnesium is reduced or lost [9].

Treatment: In patients with normal renal function, IV fluids or furosemide may be administered to promote the excretion of magnesium. In patients with symptomatic hypermagnesaemia, slow IV injection of calcium gluconate can be administered to antagonize the cardiac and neuromuscular effects of magnesium [12].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1alpha-Hydroxyvitamin D5The serum concentration of Magnesium gluconate can be increased when it is combined with 1alpha-Hydroxyvitamin D5.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Magnesium gluconate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-Aza-2,3-Dihydrogeranyl DiphosphateMagnesium gluconate can cause a decrease in the absorption of 3-Aza-2,3-Dihydrogeranyl Diphosphate resulting in a reduced serum concentration and potentially a decrease in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Magnesium gluconate.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Magnesium gluconate.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Magnesium gluconate.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Magnesium gluconate is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Magnesium gluconate.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Magnesium gluconate.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Magnesium gluconate.
Food Interactions
Not Available

References

General References
  1. Li S, Tian H: [Oral low-dose magnesium gluconate preventing pregnancy induced hypertension]. Zhonghua Fu Chan Ke Za Zhi. 1997 Oct;32(10):613-5. [PubMed:9642379]
  2. Martin RW, Perry KG Jr, Martin JN Jr, Seago DP, Roberts WE, Morrison JC: Oral magnesium for tocolysis: a comparison of magnesium gluconate and enteric-coated magnesium chloride. J Miss State Med Assoc. 1998 May;39(5):180-2. [PubMed:9610075]
  3. Grober U, Schmidt J, Kisters K: Magnesium in Prevention and Therapy. Nutrients. 2015 Sep 23;7(9):8199-226. doi: 10.3390/nu7095388. [PubMed:26404370]
  4. Makrides M, Crosby DD, Bain E, Crowther CA: Magnesium supplementation in pregnancy. Cochrane Database Syst Rev. 2014 Apr 3;(4):CD000937. doi: 10.1002/14651858.CD000937.pub2. [PubMed:24696187]
  5. Coudray C, Rambeau M, Feillet-Coudray C, Gueux E, Tressol JC, Mazur A, Rayssiguier Y: Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnes Res. 2005 Dec;18(4):215-23. [PubMed:16548135]
  6. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
  7. PubChem, Sodium Gluconate [Link]
  8. Magnesium Gluconate [Link]
  9. NIH document, Magnesium [Link]
  10. NIH Medlie, Magnesium Gluconate [Link]
  11. Mg products [Link]
  12. MIMS: Magnesium gluconate [Link]
  13. Mg Gluconate [Link]
  14. Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach [Link]
  15. Safety Data [File]
External Links
PubChem Compound
71587201
PubChem Substance
347829314
ChemSpider
28295928
ChEMBL
CHEMBL3989640
Wikipedia
Magnesium_gluconate
ATC Codes
A12CC03 — Magnesium gluconate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedTreatmentAlagille Syndrome / Biliary Atresia / Cholestasis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)673http://www.thegoodscentscompany.com/data/rw1362501.html
water solubilitySoluble in cold waterMSDS
logP-3.175http://www.thegoodscentscompany.com/data/rw1362501.html
Predicted Properties
PropertyValueSource
Water Solubility43.2 mg/mLALOGPS
logP-2ALOGPS
logP-3.4ChemAxon
logS-0.98ALOGPS
pKa (Strongest Acidic)3.39ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area141.28 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity49.11 m3·mol-1ChemAxon
Polarizability16.62 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as sugar acids and derivatives. These are compounds containing a saccharide unit which bears a carboxylic acid group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Sugar acids and derivatives
Alternative Parents
Medium-chain hydroxy acids and derivatives / Medium-chain fatty acids / Beta hydroxy acids and derivatives / Hydroxy fatty acids / Monosaccharides / Secondary alcohols / Carboxylic acid salts / Polyols / Carboxylic acids / Monocarboxylic acids and derivatives
show 6 more
Substituents
Gluconic_acid / Medium-chain hydroxy acid / Medium-chain fatty acid / Beta-hydroxy acid / Hydroxy fatty acid / Hydroxy acid / Fatty acyl / Monosaccharide / Fatty acid / Carboxylic acid salt
show 13 more
Molecular Framework
Not Available
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Blood fluke
Pharmacological action
Yes
Actions
Substrate
General Function
Hexokinase activity
Specific Function
Not Available
Gene Name
Not Available
Uniprot ID
Q26609
Uniprot Name
Hexokinase
Molecular Weight
50445.62 Da
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
Inducer
General Function
Ubiquitin protein ligase binding
Specific Function
Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with l...
Gene Name
CKB
Uniprot ID
P12277
Uniprot Name
Creatine kinase B-type
Molecular Weight
42643.95 Da
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
Inducer
General Function
Syntaxin binding
Specific Function
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility a...
Gene Name
ABL1
Uniprot ID
P00519
Uniprot Name
Tyrosine-protein kinase ABL1
Molecular Weight
122871.435 Da
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Transporter activity
Specific Function
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport comp...
Gene Name
ATP5D
Uniprot ID
P30049
Uniprot Name
ATP synthase subunit delta, mitochondrial
Molecular Weight
17489.755 Da
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Metal ion binding
Specific Function
Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates responses to increased cellular Ca(2+)/calmodulin levels (By similarity). May be involved in regu...
Gene Name
ADCY1
Uniprot ID
Q08828
Uniprot Name
Adenylate cyclase type 1
Molecular Weight
123438.85 Da
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Heme binding
Specific Function
Has guanylyl cyclase on binding to the beta-1 subunit.Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
Gene Name
GUCY1A2
Uniprot ID
P33402
Uniprot Name
Guanylate cyclase soluble subunit alpha-2
Molecular Weight
81749.185 Da
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Identical protein binding
Specific Function
Synthesis and degradation of fructose 2,6-bisphosphate.
Gene Name
PFKFB1
Uniprot ID
P16118
Uniprot Name
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1
Molecular Weight
54680.86 Da
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
8. Phosphoribosylpyrophosphate synthetase
Kind
Protein
Organism
Plasmodium falciparum
Pharmacological action
Yes
Actions
Inducer
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Steroid hormone binding
Specific Function
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates th...
Gene Name
ATP1A1
Uniprot ID
P05023
Uniprot Name
Sodium/potassium-transporting ATPase subunit alpha-1
Molecular Weight
112895.01 Da
References
  1. Swaminathan R: Magnesium metabolism and its disorders. Clin Biochem Rev. 2003 May;24(2):47-66. [PubMed:18568054]

Drug created on June 23, 2017 14:47 / Updated on November 02, 2018 07:45