In rats, the single-dose dose of simethicone (200 mg/kg) exhibits gastrointestinal regulating effects [2]. Rabbits treated with simethicone (20 mg/kg; cup; single dose) exhibit jejunal modifying effects [3].

Animal/Disease Models: Female adult Wistar rat (200–250 g) [2].
Doses: 50, 100 and 200 mg/kg.
Route of Administration: po (oral gavage); single dose.
Experimental Results: Improved colonic permeability and allergy (200 mg/kg).

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Animal/Disease Models: Adult New Zealand White rabbit (NZW) [3].
Doses: 20 mg/kg.
Route of Administration: po (oral gavage); single dose.
Experimental Results: Improved image quality scores of the jejunum without affecting the left kidney, right kidney, and gallbladder.

Absorption, Distribution and Excretion
Simethicone is not systemically absorbed and so these data are not readily available.
Simethicone is eliminated in the feces.
Simethicone is not systemically absorbed and so these data are not readily available.
Simethicone is not systemically absorbed and so these data are not readily available.
Simethicone is physiologically inert; it does not appear to be absorbed from the GI tract or to interfere with gastric secretion or absorption of nutrients. Following oral administration, the drug is excreted unchanged in feces.

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Metabolism / Metabolites
Simethicone is not systemically absorbed and so it is not metabolised by the body.

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Biological Half-Life
Simethicone is not systemically absorbed and so these data are not readily available.

Toxicity Summary
IDENTIFICATION AND USE: Simethicone is a gray, translucent, viscous liquid. Simethicone is used in the production of anti-gas tablets; lubrication and bubble free application of topical preparations; anti-whitening properties in acne and other dermatological ointments, creams and lotions; as an antifoaming agent in the manufacture of drug products made by microbial fermentations; it is used in cosmetic and toiletry products. HUMAN EXPOSURE AND TOXICITY: Unrelated case reports have been documented where simethicone was administered in conjunction with another drug as part of a prescribed treatment and an adverse event occurred. The incidences of pulmonary aspiration of gastric contents and apnea did not indicate that simethicone alone was the cause of the adverse event. The two cases of overdose were not intentional but due to incorrect dosing instructions or unknown drug interaction. ANIMAL STUDIES: In studies on the treatment of irritable bowel syndrome with rats, simethicone reduced stress-induced increase of colonic permeability and hypersensitivity to distension. In developmental toxicity study it was found that oral administration of food grade simethicone during organogenesis produced no developmental effects including teratogenicity in rabbits at dietary levels up to 2.5%.

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Protein Binding
Simethicone is not systemically absorbed and so these data are not readily available.

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Interactions
The effect of an antacid on the bioavailability of lithium carbonate was determined in six healthy men in a crossover study. The volunteers were given single 300-mg doses of lithium carbonate alone and with 30 ml of an antacid containing aluminum and magnesium hydroxides with simethicone. Blood samples were collected at various times for 0-24 hours after each dose. The plasma samples were analyzed for lithium using a spectrophotometer, and bioavailability variables were calculated from plasma lithium concentration-time curves. There were no significant differences in peak plasma lithium concentration, time to peak concentration, area under the concentration-time curve from 0 to 24 hours, first-order absorption rate constant, and first-order elimination rate constant between the two treatments. Concurrent administration of antacids and lithium carbonate should not affect lithium blood concentrations.
Carbamazepine is an anticonvulsant drug and is also used as a treatment for patients with manic-depressive illness, post-herpetic neuralgia or phantom limb pain. The drug itself has many drug interactions. Simethicone is an antifoaming agent and is reported to be an inert material with no known drug interaction with carbamazepine. We present a case of a patient who was routinely using carbamazepine 400 mg three times per day and levetiracetam 500 mg twice daily, and experienced carbamazepine overdose after exposure to simethicone. After cessation of simethicone therapy normal drug levels of carbamazepine were obtained again with the standard dose of the drug. The mechanism of interaction is unknown but the risk of overdose should be considered when prescribing simethicone to a patient who is using carbamazepine. Simethicone and carbamazepine, when taken together, may be a cause of carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.
The abilities of antacid (Mylanta II /simethicone/), sucralfate, cimetidine, and ranitidine to protect the gastric mucosa against ethanol-induced necrosis were compared in a standardized, experimental rat model. Fasted rats received pretreatment with either saline, Mylanta II, 500 mg/kg of sucralfate, 50 mg/kg of cimetidine, or 50 mg/kg of ranitidine. This was followed one hour later by intragastric administration of 2 mL of 100 percent ethanol. Gastric mucosal injury was assessed four hours after administration of ethanol by quantitation of gross mucosal necrosis, assessment of mucosal histology, and determination of intragastric blood and protein concentrations. Pretreatment with Mylanta II or sucralfate significantly reduced ethanol-induced gastric mucosal necrosis. The protective effect of sucralfate was six to 10 times greater than that of Mylanta II. H2-receptor antagonists increased ethanol-induced gastric mucosal necrosis.
Alverine, an antispasmodic agent for the treatment of irritable bowel syndrome (IBS), may be combined with simethicone, a protective agent of the mucosa. Stress is a major factor triggering abdominal pain in IBS and causing hypersensitivity to colonic distension in animals through an increased colonic permeability. The antinociceptive effects of alverine and simethicone, separately or in association, were evaluated on stress-induced colonic hypersensitivity to distension in rats. The influence of simethicone on altered permeability was also tested. Groups of 8-10 female adult Wistar rats (200-250 g) housed individually were used. Gut paracellular permeability was evaluated after 2 hr of partial restraint stress using oral gavage with (51)Cr-EDTA and 24 hr of urine collection. The number of abdominal cramps during colonic distension was evaluated in animals equipped with electrodes on their abdominal striated muscles. At 200 mg/kg p.o. twice a day, but not at lower doses, simethicone reduced stress-induced increase of colonic permeability and hypersensitivity to distension. Administered alone at 10 mg/kg p.o., alverine also reduced stress-induced hypersensitivity to distension; lower doses were inactive. However, alverine administered at an inactive dose with simethicone suppressed stress-induced hypersensitivity to distension. We conclude that both simethicone and alverine have visceral antinociceptive effects by two different mechanisms and that simethicone exerts a potentiating effect on the antinociceptive action of alverine.

[1]. Evaluation of simethicone for the treatment of postoperative abdominal discomfort in infants. J Clin Anesth. 1998 Mar;10(2):91-4.

[2]. Influence of simethicone and alverine on stress-induced alterations of colonic permeability and sensitivity in rats: beneficial effect of their association. J Pharm Pharmacol. 2013 Apr;65(4):567-73.

[3]. Influence of simethicone and fasting on the quality of abdominal ultrasonography in New Zealand White rabbits. Acta Vet Scand. 2017 Jul 17;59(1):48.

Simethicone is a silicon based surfactant that decreases the surface tension of gastrointestinal gas bubbles to facilitate their elimination. It has a favourable safety profile as it is not systemically absorbed. Simethicone has been in use since the 1940s but was granted FDA approval in 1952.
Simethicone is a mixture of polydimethylsiloxanes with antifoaming and anti-bloating effects. Simethicone reduces the surface tension of gas bubbles causing them to coalesce into larger bubbles that can be passed more easily by belching or flatulence.
A poly(dimethylsiloxane) which is a polymer of 200-350 units of dimethylsiloxane, along with added silica gel. It is used as an antiflatulent, surfactant, and ointment base.

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Drug Indication
Simethicone is indicated for the treatment of bloating, pressure, and cramps caused by gas. Simethicone is also used as part of bowel preparation for colonoscopies.

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Mechanism of Action
Simethicone is a surfactant that decreases the surface tension of gas bubbles in the gastrointestinal tract, more easily allowing gas to exit the body.
The clinical use of simethicone is based on its antifoam properties. Silicone antifoams spread on the surface of aqueous liquids, forming a film of low surface tension and thus causing collapse of foam bubbles. Simethicone reportedly allows mucus-surrounded gas bubbles in the GI tract to coalesce and be expelled.

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Therapeutic Uses
Antifoaming Agents; Emollients
/EXPERIMENTAL THERAPY/ Currently, there is no standardized protocol for bowel preparation before small bowel capsule endoscopy (SBCE). This study aimed to investigate the effect of simethicone combined with polyethylene glycol (PEG) on the visualization quality (VQ) of the SBCE in patients with or without known or suspected Crohn's disease (CD). This observational, prospective, single-center study included consecutive patients undergoing a SBCE between 2007 and 2008. Patients received either a standard bowel cleansing preparation of 2 L PEG and 80 mg simethicone orally 12 and 1 h before SBCE respectively (Group A) or only PEG (Group B). VQ, based on scores for luminal bubbles in frames taken from the small intestine, examination completeness, SBCE diagnostic yield, gastric and small bowel transit times were recorded. Of the 115 patients finally included (Group A, n=56 and Group B, n=59) the cecum was visualized in 103 (89.6%). Simethicone overall improved the VQ in the proximal [OR: 2.43 (95%CI: 1.08-5.45), P=0.032] but not in the distal bowel segment (P=0.064). Nevertheless, this effect was not observed in patients undergoing SBCE for either known or suspected CD. Simethicone as an adjunct to PEG for bowel preparation in patients undergoing SBCE significantly improved the VQ in non-CD patients.
Simethicone is used as an adjunct in the symptomatic treatment of flatulence, functional gastric bloating, and postoperative gas pains. For self-medication, the drug is used as an antiflatulent to relieve symptoms commonly referred to as gas, including upper GI bloating, pressure, fullness, or stuffed feeling. Simethicone also has been used prior to gastroscopy to enhance visualization and prior to radiography of the intestine to reduce gas shadows. Although there is gastroscopic evidence that simethicone aids in the elimination of gas from the GI tract and reduces postoperative gas pains, the relationship of gas accumulation to what patients commonly refer to as symptoms of gas under ordinary conditions is not clear; however, the drug also has been shown to be effective in relieving these symptoms. Preparations of simethicone with antacids, antispasmodics, or digestive enzymes are available, but use of inflexible combinations of drugs is often unwarranted, and these products have not been well evaluated.
Although simethicone is an effective antiflatulent, there currently is no conclusive evidence that immediate postprandial upper abdominal distress (IPPUAD) is caused by excessive gas, despite the fact that many patients commonly attribute symptoms of the distress to gas. In addition, current data are insufficient to establish the efficacy of simethicone for the symptomatic relief of IPPUAD, a symptom complex that occurs within 30 minutes after a meal and consists of sensations of GI bloating, distention, fullness, or pressure with upper abdominal discomfort but not aerophagia or hyperacidity.
For more Therapeutic Uses (Complete) data for Simethicone (11 total), please visit the HSDB record page.

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Drug Warnings
... Simethicone and carbamazepine, when taken together, may be a cause of carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.
Although no data are available on the use of simethicone during breastfeeding, it is known that simethicone is not absorbed orally. Therefore, it cannot be transferred to breastmilk. It is also used safely in breastfed infants. No special precautions are required.
Simethicone is apparently nontoxic, and no adverse effects have been reported.

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Pharmacodynamics
Simethicone decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion. It has a short duration of action as it is generally given as needed, and a wide therapeutic index as it is not systemically absorbed.

(C2H6OSI)N.(SIO2)M

238.461225032806

238.051

8050-81-5

6433516

Colorless to off-white liquid

1 g/mL at 20ºC

96.5ºC at 760 mmHg

6.3ºC

5 mm Hg ( 20 °C)

n20/D 1.406

1.567

0

4

3

13

125

0

O=[Si]=O.CO[Si](O[Si](C)(C)C)(C)C

AMTWCFIAVKBGOD-UHFFFAOYSA-N

InChI=1S/C6H18O2Si2.O2Si/c1-7-10(5,6)8-9(2,3)4;1-3-2/h1-6H3;

alpha-(Trimethylsilyl)-omega-methylpoly(oxy(dimethylsilylene)), mixture with silicon dioxide

Simethicone Simeticone Disflatyl SimethiconePhazyme

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

DMSO : ~100 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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