Absorption, Distribution and Excretion
Maximal absorption occurs at doses of 500 mg or less taken with food. Oral bioavailability depends on intestinal pH, the presence of food and dosage.
Excreted mainly in the feces. The majority of renally filtered calcium is reabsorbed in the ascending limb of the loop of Henle and the proximal and distal convoluted tubules. Also secreted by sweat glands.
Calcium is rapidly distributed taken up by skeletal tissues following absorption and distribution into extracellular fluids. Bone contains 99% of the body's calcium and the remaining 1% is approximately equally distributed between intracellular and extracellular fluids.
Calcium absorption is best when a person consumes no more than 500 mg at one time. So a person who takes 1,000 mg/day of calcium from supplements, for example, should split the dose rather than take it all at once.
Amount of calcium absorbed from calcium carbonate is usually stated to be 10%, but ... depends upon amount of gastric acid; in 1 study, 0-2% of single 2 g dose was ... absorbed in achlorhydric persons, 9-16% in normal subjects, and 11-37% in patients with peptic ulcer ...
Fraction absorbed seems to be nearly the same when CaCO3 is given chronically in daily doses of 20 g /as when it is given in single 2 g dose/. ... Amount absorbed probably reaches a plateau at a dose of about 20 g.
... Increased calcium excretion almost always follows admin of antacid doses of calcium carbonate ...
For more Absorption, Distribution and Excretion (Complete) data for CALCIUM CARBONATE (15 total), please visit the HSDB record page.

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Metabolism / Metabolites
None.
After ingestion /of CaCO3 tablets/, it is converted to sol calcium salts in stomach, and calcium is thereby made available for absorption.

Interactions
... A mixture of 2 parts magnesium oxide and 1 part calcium carbonate produces relatively normal stool for many patients.
Milk-alkali syndrome may occur after prolonged admin of calcium carbonate with concomitant use of sodium bicarbonate and/or homogenized milk containing Vit D.
Certain anions in antacids (carbonate and hydroxide) ... are thought to form insoluble complexes when combined with iron. A study evaluating the effect of antacids and iron absorption used patients with mild iron deficiency and found that when Mylanta II (5 mL) was given with 10 mg of iron, the increase in plasma iron seen two hours after the dose was not significantly different from the iron level seen two hours after a control dose. ... calcium carbonate 500 mg also decreased the two-hour plasma levels, with serum iron levels attaining only one-third of the control dose.
Concurrent use of excessive amounts of /alcohol, caffeine (usually more than 8 cups of coffee a day), or tobacco/ has been reported to decrease calcium absorption.
For more Interactions (Complete) data for CALCIUM CARBONATE (45 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse oral 6450 mg/kg bw
LD50 Rat oral 6450 mg/kg

Calcium carbonate appears as white, odorless powder or colorless crystals. Practically insoluble in water. Occurs extensive in rocks world-wide. Ground calcium carbonate (CAS: 1317-65-3) results directly from the mining of limestone. The extraction process keeps the carbonate very close to its original state of purity and delivers a finely ground product either in dry or slurry form. Precipitated calcium carbonate (CAS: 471-34-1) is produced industrially by the decomposition of limestone to calcium oxide followed by subsequent recarbonization or as a by-product of the Solvay process (which is used to make sodium carbonate). Precipitated calcium carbonate is purer than ground calcium carbonate and has different (and tailorable) handling properties.
Calcium carbonate is a calcium salt with formula CCaO3. It has a role as an antacid, a food colouring, a food firming agent and a fertilizer. It is a calcium salt, a carbonate salt, a one-carbon compound and an inorganic calcium salt.
Calcium carbonate is an inorganic salt used as an antacid. It is a basic compound that acts by neutralizing hydrochloric acid in gastric secretions. Subsequent increases in pH may inhibit the action of pepsin. An increase in bicarbonate ions and prostaglandins may also confer cytoprotective effects. Calcium carbonate may also be used as a nutritional supplement or to treat hypocalcemia.
Calcium Carbonate is the carbonic salt of calcium (CaCO3). Calcium carbonate is used therapeutically as a phosphate buffer in hemodialysis, as an antacid in gastric hyperacidity for temporary relief of indigestion and heartburn, and as a calcium supplement for preventing and treating osteoporosis. (NCI04)
Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.
See also: Calcium (has active moiety); Calcium Cation (has active moiety); Carbonate Ion (has active moiety) ... View More ...

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Drug Indication
For relief of heartburn and acid indigestion. May also be used as a nutritional supplement or to treat hypocalcemia.

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Mechanism of Action
Calcium carbonate is a basic inorganic salt that acts by neutralizing hydrochloric acid in gastric secretions. It also inhibits the action of pepsin by increasing the pH and via adsorption. Cytoprotective effects may occur through increases in bicarbonate ion (HCO₃^-) and prostaglandins. Neutralization of hydrochloric acid results in the formation of calcium chloride, carbon dioxide and water. Approximately 90% of calcium chloride is converted to insoluble calcium salts (e.g. calcium carbonate and calcium phosphate).

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Therapeutic Uses
Mesh Heading: Antacids
/EXPL THER/ The aim of the present study was to test the hypothesis that a fibrin matrix enhances the osteogenic differentiation and expression of vascular endothelial growth factor (VEGF) by human bone marrow stromal cells (hBMSCs) seeded into mineralised scaffolds. Porous calcium carbonate scaffolds were droplet seeded with hBMSCs using a matrix containing 3 % fibrinogen and cultured for 3 weeks. Seeded scaffolds without the fibrin matrix served as controls. The scaffolds were evaluated, using undecalcified thick sections, for fluorescence staining for nuclei, osteocalcin (OC) and VEGF. The sections were systematically scanned using optical sectioning and three dimensional distributions of cells and positive staining indicating expression of OC and VEGF were reconstructed from the z-stacks. The fibrin matrix maintained a significantly higher level of cell numbers after 2 d and 1 week and delayed the onset of osteogenic differentiation while sustaining a significantly higher level of OC and VEGF expression after 2 and 3 weeks, starting from the periphery of the scaffolds. There was a decrease in cell density from the periphery to the centre of the scaffolds in both groups. The percentage of cells expressing OC and VEGF was significantly different between the centre and the periphery of the scaffolds in the fibrin(+) group but not in the controls. It is concluded that the fibrin matrix used appears to be a useful adjunct for supporting and sustaining osteogenic and angiogenic activity of hBMSCs in tissue engineered constructs. This could help to improve their performance in a clinical setting.
/EXPL THER/ Thirty coral-derived calcium carbonate-based macroporous constructs with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) were implanted in the rectus abdominis of three adult non-human primate Papio ursinus to investigate the intrinsic induction of bone formation. Macroporous constructs with 125 ug human recombinant osteogenic protein-1 (hOP-1) or 125 ug human recombinant transforming growth factor-beta(3) (hTGF-beta(3)) were also implanted. The potential synergistic interaction between morphogens was tested by implanting binary applications of hOP-1 and hTGF-beta(3) 5:1 by weight, respectively. To evaluate the role of osteoclastic activity on the implanted macroporous surfaces, coral-derived constructs were pre-loaded with 0.24 mg of bisphosphonate zoledronate (Zometa). To correlate the morphology of tissue induction with osteogenic gene expression and activation, harvested specimens on day 90 were analyzed for changes in OP-1 and TGF-beta(3) mRNA synthesis by quantitative real-time polymerase chain reaction (qRT-PCR). The induction of bone formation in 7% HA/CC solo correlated with OP-1 expression. Massive bone induction formed by binary applications of the recombinant morphogens. Single applications of hOP-1 and hTGF-beta(3) also resulted in substantial bone formation, not comparable however to synergistic binary applications. Zoledronate-treated macroporous constructs showed limited bone formation and in two specimens bone formation was altogether absent; qRT-PCR showed a prominent reduction of OP-1 gene expression whilst TGF-beta(3) expression was far greater than OP-1. The lack of bone formation by zoledronate-treated specimens indicates that osteoclastic activity on the implanted coral-derived constructs is critical for the spontaneous induction of bone formation. Indirectly, zoledronate-treated samples showing lack of OP-1 gene expression and absent or very limited bone formation by induction confirm that the spontaneous induction of bone formation by coral-derived macroporous constructs is initiated by secreted BMPs/OPs, in context the OP-1 isoform.
/EXPL THER/ Calcium is an essential cotherapy in osteoporosis treatment. The relative effectiveness of various calcium salts for this purpose is uncertain. Many older women with osteoporosis have phosphorus intakes of <70% of the Recommended Dietary Allowance. /The study's/ objective was to test the hypothesis that calcium phosphate would better support anabolic bone building than would calcium carbonate. This study was a 12-mo, randomized, positive-comparator, 2-arm, single-blind clinical trial in 211 patients treated with teriparatide who consumed <1000 mg phosphorus/d. Participants were randomly assigned to receive, in addition to teriparatide and 1000 IU cholecalciferol, 1800 mg calcium/d as either tricalcium phosphate or calcium carbonate. The primary endpoints were changes in lumbar spine and total hip bone mineral densities (BMDs); secondary endpoints were changes in bone resorption biomarkers and serum and urine calcium and phosphorus concentrations. In the combined group, the lumbar spine BMD increased by 7.2%, and total hip BMD increased by 2.1% (P < 0.01 for both). However, there was no significant difference between calcium-treatment groups, and there were no significant between-group differences in serum calcium and phosphorus concentrations or in urine calcium concentrations. Bone resorption biomarkers increased in both groups, as expected with teriparatide, but the increases in the 2 calcium groups did not differ significantly.Tricalcium phosphate and calcium carbonate appear to be approximately equally effective in supporting bone building with a potent anabolic agent; phosphate salt may be preferable in patients with restricted phosphorus intakes.
For more Therapeutic Uses (Complete) data for CALCIUM CARBONATE (20 total), please visit the HSDB record page.

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Drug Warnings
Large doses of calcium carbonate (above 2 g) increase gastric secretion for a period of time that considerably outlasts elevation of pH. ... With single doses below 2 g, this effect is negligible.
After ingestion /of CaCO3 tablets/, it is converted to sol calcium salts in bowel, and calcium is thereby made available for absorption. Patients with achlorhydria may not solubilize calcium from ... preparation.
Gastric hypersecretory action is counter productive and may possibly account for various reports that calcium carbonate is less efficacious than other antacids. Calcium carbonate has been known to cause fecal concretions.
Constipating effects and chalky taste of calcium carbonate are clinically disadvantageous.
For more Drug Warnings (Complete) data for CALCIUM CARBONATE (23 total), please visit the HSDB record page.

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Pharmacodynamics
Gastric-peptic disease occurs as a result of an imbalance between protective factors, such as mucus, bicarbonate, and prostaglandin secretion, and aggressive factors, such as hydrochloric acid, pepsin, and Helicobacter pylori (H. pylori). Antacids work by restoring acid-base balance, attenuating the pepsin activity and increasing bicarbonate and prostaglandin secretion. The acid-neutralizing capacity of calcium carbonate is 58 mEq/15 ml. When used as a nutritional supplement, calcium carbonate acts by directly increasing calcium stores within the body.

CCAO3

100.09

101.962

471-34-1

10112

White hexagonal crystals or powder (Calcite); white orthrombic crystals or powder (Argonite); colorless hexagonal crystals (vaterite)

2.93 g/mL at 25 °C(lit.)

800 °C

825 °C

197ºC

1.6583

0

3

0

5

18.8

0

[Ca+2].[O-]C(=O)[O-]

VTYYLEPIZMXCLO-UHFFFAOYSA-L

InChI=1S/CH2O3.Ca/c2-1(3)4;/h(H2,2,3,4);/q;+2/p-2

calcium;carbonate

BRT 1500; Aeromatt; Calcium carbonate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)