Absorption, Distribution and Excretion
When taken with food, doses of 500 mg or less achieve maximum absorption. Oral bioavailability depends on intestinal pH, the presence of food, and the dose. It is primarily excreted in feces. Most calcium filtered by the kidneys is reabsorbed in the ascending limb of the loop of Henle and in the proximal and distal tubules. Calcium is also secreted by sweat glands. After absorption, calcium is rapidly distributed, absorbed by bone tissue, and distributed into the extracellular fluid. Bones contain 99% of the body's calcium, with the remaining 1% distributed roughly evenly in the intracellular and extracellular fluids. Calcium absorption is optimal when ingested in doses not exceeding 500 mg. For example, someone taking a 1000 mg calcium supplement daily should divide the dose into several smaller doses rather than taking it all at once.
It is generally believed that the absorption rate of calcium carbonate is 10%, but… this depends on the amount of stomach acid; in one study, the absorption rate of a single dose of 2 grams of calcium carbonate was 0-2% in people with low stomach acid, 9-16% in normal individuals, and 11-37% in patients with peptic ulcers…
The absorption rate of long-term daily intake of 20 grams of calcium carbonate appears to be almost the same as that of a single dose of 2 grams. Absorption may plateau at a dose of approximately 20 grams.
…After taking antacid doses of calcium carbonate, an increase in calcium excretion almost always occurs…
For more complete data on the absorption, distribution, and excretion of calcium carbonate (out of 15), please visit the HSDB records page.

---

Metabolism/Metabolites
None.
After taking calcium carbonate tablets, it is converted into soluble calcium salts in the stomach, allowing calcium to be absorbed.

Interactions
A mixture of 2 parts magnesium oxide and 1 part calcium carbonate can result in relatively normal stool characteristics in many patients. Long-term use of calcium carbonate in conjunction with sodium bicarbonate and/or homogenized milk containing vitamin D may lead to lactic acid syndrome. Certain anions (carbonate and hydroxide) in antacids are believed to form insoluble complexes when bound to iron. A study assessing the effects of antacids on iron absorption, including patients with mild iron deficiency, found that when 5 ml of Mylanta II was taken concurrently with 10 mg of iron, the increase in plasma iron levels two hours after administration was not significantly different from that after administration of the control dose. 500 mg of calcium carbonate also reduced plasma concentrations two hours later, with serum iron levels reaching only one-third of the control dose. Excessive alcohol consumption, caffeine intake (typically more than 8 cups of coffee per day), or smoking has been reported to reduce calcium absorption. For more complete data on interactions with calcium carbonate (45 in total), please visit the HSDB records page.

---

Non-human toxicity values
Oral LD50 in mice: 6450 mg/kg body weight
Oral LD50 in rats: 6450 mg/kg body weight

Calcium carbonate is a white, odorless powder or colorless crystal, almost insoluble in water, and widely found in rocks worldwide. Ground calcium carbonate (CAS: 1317-65-3) is obtained directly from limestone mining. The extraction process preserves the calcium carbonate close to its original purity, yielding a fine powder or slurry product. Precipitated calcium carbonate (CAS: 471-34-1) is industrially produced by decomposing limestone into calcium oxide, followed by recarbonation, or as a byproduct of the Solvay process (used to produce sodium carbonate). Precipitated calcium carbonate has a higher purity than ground calcium carbonate and offers different (customizable) handling characteristics. Calcium carbonate is a calcium salt with the chemical formula CCaO₃. It is used as an antacid, food coloring agent, food thickener, and fertilizer. It is a calcium salt, carbonate, one-carbon compound, and inorganic calcium salt. Calcium carbonate is an inorganic salt used as an antacid. It is an alkaline compound that works by neutralizing hydrochloric acid in gastric juice. The subsequent increase in pH may inhibit the activity of pepsin. Increased bicarbonate ions and prostaglandins may also have cytoprotective effects. Calcium carbonate is also used as a nutritional supplement or to treat hypocalcemia. Calcium carbonate is the carbonate of calcium carbonate (CaCO3). Calcium carbonate is used therapeutically as a phosphate buffer in hemodialysis, as an antacid to treat hyperacidity, to temporarily relieve indigestion and heartburn, and as a calcium supplement for the prevention and treatment of osteoporosis. (NCI04) Calcium carbonate (CaCO3). A naturally occurring, odorless, tasteless powder or crystal. It is used as a phosphate buffer and calcium supplement for hemodialysis patients. See also: calcium (containing the active fraction); calcium ions (containing the active fraction); carbonate ions (containing the active fraction)... See more...

---

Pharmaceutical Indications
For the relief of heartburn and acid reflux. Also used as a nutritional supplement or to treat hypocalcemia.

---

Mechanism of Action
Calcium carbonate is an alkaline inorganic salt whose mechanism of action is by neutralizing hydrochloric acid in gastric juice. It can also inhibit pepsin activity by increasing pH and adsorption. Cell protection may occur by increasing the levels of bicarbonate ions (HCO3-) and prostaglandins. Neutralization with hydrochloric acid produces calcium chloride, carbon dioxide, and water. Approximately 90% of the calcium chloride is converted into insoluble calcium salts (such as calcium carbonate and calcium phosphate).

---

Therapeutic Uses
MeSH Title: Antacids
/EXPL THER/ This study aimed to verify the hypothesis that fibrin matrix can enhance osteogenic differentiation and vascular endothelial growth factor (VEGF) expression in human bone marrow mesenchymal stem cells (hBMSCs) seeded on mineralized scaffolds. hBMSCs were seeded dropwise onto porous calcium carbonate scaffolds and cultured for 3 weeks using a matrix containing 3% fibrinogen. A seeded scaffold without fibrin matrix served as a control. Nucleus, osteocalcin (OC), and VEGF expression in the scaffolds were assessed by fluorescent staining using undecalcified thick sections. Systematic scanning of tissue sections was performed using optical sectioning techniques, and the three-dimensional distribution of cells and the expression of OC and VEGF positive staining were reconstructed from z-axis stacked images. The fibrin matrix maintained significantly higher cell numbers at 2 days and 1 week, delayed osteogenic differentiation, and maintained significantly higher OC and VEGF expression levels at 2 and 3 weeks, with these expression levels increasing from the periphery of the scaffold. Cell density in both groups gradually decreased from the periphery to the center of the scaffold. In the fibrin(+) group, there was a significant difference in the percentage of cells expressing OC and VEGF between the center and periphery of the scaffold, while no such difference was observed in the control group. The conclusion is that the fibrin matrix used appears to be an effective adjunct to support and maintain the osteogenic and angiogenic activity of hBMSCs in tissue-engineered constructs. This may contribute to improving their performance in clinical settings.
/EXPL THER/ Thirty coral-derived calcium carbonate-based macroporous structures (converted to hydroxyapatite via limited hydrothermal treatment, with an HA/CC content of 7%) were implanted into the rectus abdominis muscles of three adult non-human primates (Papio ursinus) to investigate their intrinsic induction of bone formation. Macroporous structures containing either 125 μg of recombinant human osteogenic protein-1 (hOP-1) or 125 μg of recombinant human transforming growth factor-β3 (hTGF-β3) were also implanted. Potential synergistic effects between morphogenetic elements were tested by implanting a binary mixture of hOP-1 and hTGF-β3 at a weight ratio of 5:1. To assess the role of osteoclast activity on the implanted macroporous surface, the coral-derived constructs were preloaded with 0.24 mg of the bisphosphonate zoledronic acid (Zometa). To link tissue-induced morphogenesis with osteogenic gene expression and activation, samples were collected on day 90, and changes in OP-1 and TGF-β3 mRNA synthesis were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Bone formation induced by 7% HA/CC alone was associated with OP-1 expression. Dual application of recombinant morphogenetic agents induced significant bone formation. Application of hOP-1 and hTGF-β3 alone also resulted in significant bone formation, but the effect was inferior compared to synergistic dual application. Zoledronic acid-treated macroporous constructs showed limited bone formation, with no bone formation in either sample; qRT-PCR results showed significantly reduced OP-1 gene expression, while TGF-β3 expression was much higher than OP-1. The lack of bone formation in the zoledronic acid-treated group suggests that osteoclast activity on the implanted coral-derived constructs is crucial for spontaneous bone formation induction. Indirectly, the absence of OP-1 gene expression and minimal or absent post-induced bone formation in the zoledronic acid-treated group confirmed that spontaneous bone formation induced by coral-derived macroporous constructs is initiated by secreted BMPs/OPs (especially the OP-1 subtype). Calcium is an essential adjunct therapy in the treatment of osteoporosis. The relative efficacy of various calcium salts for this purpose remains uncertain. Many older women with osteoporosis have phosphorus intakes below 70% of the recommended dietary intake. This study aimed to verify the hypothesis that calcium phosphate promotes bone anabolism more effectively than calcium carbonate. This 12-month randomized, positive-controlled, two-arm, single-blind clinical trial enrolled 211 patients receiving teriparatide with a daily phosphorus intake <1000 mg. Subjects were randomly assigned to two groups, receiving either teriparatide or 1000 IU cholecalciferol, supplemented with 1800 mg/day of calcium, either tricalcium phosphate or calcium carbonate. The primary endpoint was changes in lumbar spine and total hip bone mineral density (BMD); secondary endpoints were changes in bone resorption biomarkers and serum and urinary calcium and phosphorus concentrations. In the combination therapy group, lumbar spine BMD increased by 7.2% and total hip BMD increased by 2.1% (both P < 0.01). However, there were no significant differences between calcium therapy groups, nor were there significant differences in serum calcium and phosphorus concentrations or urinary calcium concentrations between groups. As expected, bone resorption biomarkers increased in both groups after teriparatide treatment, but the increase was not significantly different between the two calcium therapy groups. Tricalcium phosphate and calcium carbonate appear to have similarly potent anabolic effects in promoting bone growth; phosphate may be more suitable for patients with limited phosphorus intake. For more complete data on the therapeutic uses of calcium carbonate (20 types), please visit the HSDB record page. Drug Warnings: High doses of calcium carbonate (more than 2 grams) can increase gastric acid secretion for a duration far exceeding the pH elevation. ...This effect is negligible when the single dose is less than 2 grams. After taking calcium carbonate tablets, the calcium carbonate is converted into soluble calcium salts in the intestines, allowing calcium to be absorbed. Patients with hypoacidity may not be able to dissolve the calcium in calcium supplements. Excessive stomach acid secretion can be counterproductive, which may explain why some reports suggest that calcium carbonate is less effective than other antacids. Calcium carbonate is known to cause fecal stones. The constipating effect and chalky smell of calcium carbonate are clinically undesirable. For more complete data on drug warnings for calcium carbonate (23 in total), please visit the HSDB record page.

---

Pharmacodynamics
The occurrence of gastric digestive disorders is due to an imbalance between protective factors (such as mucus, bicarbonate, and prostaglandin secretion) and aggressive factors (such as hydrochloric acid, pepsin, and Helicobacter pylori). Antacids work by restoring acid-base balance, reducing pepsin activity, and increasing bicarbonate and prostaglandin secretion. Calcium carbonate has an acid-neutralizing capacity of 58 mEq/15 mL. When used as a nutritional supplement, calcium carbonate works by directly increasing the body's calcium stores.

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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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