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 absorbed systemically, therefore these data are not readily available. Simethicone is excreted in feces. Simethicone is not absorbed systemically, therefore these data are not readily available. Simethicone is not absorbed systemically, therefore these data are not readily available. Simethicone is physiologically inert; it does not appear to be absorbed by the gastrointestinal tract and does not interfere with gastric juice secretion or nutrient absorption. After oral administration, the drug is excreted unchanged in feces. Metabolism/Metabolites Simethicone is not absorbed systemically and therefore is not metabolized by the body. Biological Half-Life Simethicone is not absorbed systemically, therefore these data are not readily available.

Toxicity Summary
Identification and Uses: Simethicone is a gray, translucent, viscous liquid. It is used in the production of antiflatulent tablets; as a lubricant and antifoaming agent in topical preparations; in acne and other dermatological ointments, creams, and lotions for anti-leukoplakia effects; as an antifoaming agent in the production of microbial fermentation drugs; and also in cosmetics and toiletries. Human Exposure and Toxicity: Documented case reports have documented adverse events when simethicone was used in combination with other prescribed medications. The occurrence of aspiration of gastric contents into the lungs and respiratory arrest suggests that simethicone was not the sole cause of these adverse events. These two cases of overdose were not intentional but rather due to incorrect medication instructions or unknown drug interactions. Animal Studies: In rat studies of irritable bowel syndrome, simethicone reduced stress-induced increases in colonic permeability and hypersensitivity to distension. In developmental toxicity studies, oral administration of food-grade simethicone during organogenesis, at dietary levels up to 2.5% in rabbits, did not reveal any developmental effects, including teratogenicity. Protein Binding: Simethicone is not systemically absorbed, making data on this aspect difficult to obtain. Interactions: In a crossover study, researchers determined the effect of antacids on the bioavailability of lithium carbonate. Subjects in six healthy men received either a single dose of 300 mg lithium carbonate (alone) or 30 ml of an antacid containing aluminum hydroxide, magnesium hydroxide, and simethicone. Blood samples were collected at different time points within 0–24 hours after each administration. Lithium levels in plasma samples were analyzed using a spectrophotometer, and bioavailability parameters were calculated based on plasma lithium concentration-time curves. There were no significant differences between the two treatment regimens in terms of peak plasma lithium concentration, time to peak, area under the concentration-time curve from 0 to 24 hours, first-order absorption rate constant, and first-order elimination rate constant. Concomitant administration of antacids and lithium carbonate should not affect blood lithium concentrations. Carbamazepine is an anticonvulsant and is also used to treat bipolar disorder, postherpetic neuralgia, or phantom limb pain. This drug has several drug interactions. Simethicone is an antifoaming agent and has been reported as an inert substance; no drug interaction between simethicone and carbamazepine has been found to date. We report a case of a patient who routinely took carbamazepine 400 mg three times daily and levetiracetam 500 mg twice daily. The patient experienced a carbamazepine overdose after taking simethicone. After discontinuing simethicone, the patient resumed the standard dose of carbamazepine, and blood concentrations returned to normal. The mechanism of their interaction is currently unclear, but the risk of overdose should be considered when prescribing simethicone to patients taking carbamazepine. Concomitant use of simethicone and carbamazepine may lead to carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to patients taking carbamazepine. This study used a standardized experimental rat model to compare the protective effects of antacids (Mylanta II/simethicone), sucralfate, cimetidine, and ranitidine against ethanol-induced gastric mucosal necrosis. Fasted rats were pretreated with saline, Mylanta II, 500 mg/kg sucralfate, 50 mg/kg cimetidine, or 50 mg/kg ranitidine, respectively. One hour later, 2 mL of 100% ethanol was administered by gavage. Four hours after ethanol administration, gastric mucosal damage was assessed by quantitative analysis of the mucosal necrosis area, evaluation of mucosal histology, and measurement 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 6 to 10 times that of Mylanta II. H2 receptor antagonists exacerbated ethanol-induced gastric mucosal necrosis.
Avermectin is an antispasmodic drug used to treat irritable bowel syndrome (IBS) and can be used in combination with the mucosal protectant simethicone. Stress is a major factor inducing abdominal pain in IBS and can lead to hypersensitivity to colonic dilatation in animals by increasing colonic permeability. This study evaluated the analgesic effects of avermectin and simethicone alone or in combination on stress-induced hypersensitivity to colonic dilatation in rats and tested the effect of simethicone on changes in colonic permeability. Eight to ten female adult Wistar rats (200-250 g) were housed alone. Peri-intestinal cell permeability was assessed 2 hours after partial restraint stress using (51)Cr-EDTA gavage, and 24-hour urine was collected. Electrodes were implanted in the abdominal striated muscles to assess the number of abdominal spasms during colonic dilatation. Simethicone administered twice daily by gavage at a dose of 200 mg/kg reduced stress-induced increases in colonic permeability and hypersensitivity to dilatation, but lower doses were ineffective. Oral administration of 10 mg/kg avermectin alone reduced stress-induced hypersensitivity to distension; lower doses were ineffective. However, combined use of an ineffective dose of avermectin with simethicone inhibited stress-induced hypersensitivity to distension. We conclude that both simethicone and avermectin exert visceral analgesia through two different mechanisms, and that simethicone enhances the analgesic effect of avermectin.

[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 silicone-based surfactant that reduces the surface tension of gas bubbles in the gastrointestinal tract, thereby promoting their expulsion. It has a good safety profile because it is not absorbed systemically. Simethicone has been used since the 1940s, but was not approved by the FDA until 1952. Simethicone is a mixture of polydimethylsiloxanes with antifoaming and antiflatulent properties. It reduces the surface tension of gas bubbles, causing them to aggregate into larger bubbles, making them easier to expel through burping or flatulence. Polydimethylsiloxanes are polymers composed of 200-350 dimethylsiloxane units with added silica gel. It can be used as an antiflatulent agent, surfactant, and ointment base. Pharmacological Indications: Simethicone is indicated for the treatment of bloating, abdominal pressure, and cramps caused by gas. It is also used for bowel preparation before colonoscopy. Mechanism of Action: Simethicone is a surfactant that reduces the surface tension of gas bubbles in the gastrointestinal tract, making it easier for gas to be expelled.
The clinical application of simethicone is based on its antifoaming properties. Silicone antifoamers diffuse on the surface of aqueous liquids, forming a thin film with low surface tension, thereby causing foam bubbles to burst. Simethicone has been reported to cause mucus-encapsulated bubbles in the gastrointestinal tract to coalesce and be expelled.

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Therapeutic Uses
Antifoaming agent; emollient
/Experimental Treatment/ 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 image quality (VQ) of small bowel capsule endoscopy (SBCE) in patients with known or suspected Crohn's disease (CD). This prospective, single-center observational study included patients who underwent consecutive SBCE examinations between 2007 and 2008. Patients were randomly assigned to two groups: Group A received 2 liters of PEG and 80 mg of simethicone orally 12 hours before the SBCE examination, while Group B received only PEG orally. The study recorded ventilation quality (VQ), examination completeness, SBCE diagnostic rate, and gastric and small bowel transit time based on intraluminal bubble scores in small bowel images. A total of 115 patients were included (56 in group A and 59 in group B), of whom the cecum was observable in 103 (89.6%). Simethicone generally improved the ventilation/perfusion ratio (VQ) in the proximal bowel [OR: 2.43 (95% CI: 1.08–5.45), P = 0.032], but had no effect on the distal bowel (P = 0.064). However, this effect was not observed in patients with known or suspected Crohn's disease (CD) undergoing small bowel capsule endoscopy (SBCE). In non-CD patients undergoing SBCE, simethicone as an adjunct to polyethylene glycol (PEG) for bowel preparation significantly improved VQ. Simethicone can be used as an adjunct for the treatment of flatulence, functional flatulence, and postoperative flatulence and pain. For self-medication, this medication can be used as an anti-flatulence agent to relieve symptoms commonly referred to as "bloating," including upper gastrointestinal bloating, pressure, fullness, or congestion. Simethicone has also been used before gastroscopy to enhance visualization and before intestinal X-rays to reduce gas shadows. Although evidence from gastroscopy suggests that simethicone helps clear gastrointestinal gas and reduce postoperative bloating pain, the relationship between gas accumulation and the bloating symptoms that patients typically experience under normal circumstances is unclear; however, the medication has been shown to effectively relieve these symptoms. Combination formulations of simethicone with antacids, antispasmodics, or digestive enzymes are currently available on the market, but using single-drug combinations is generally unnecessary, and the efficacy of these products has not been fully evaluated. Although simethicone is an effective anti-flatulence agent, there is currently no conclusive evidence that immediate postprandial upper abdominal discomfort (IPPUAD) is caused by excess gas, although many patients often attribute their discomfort to bloating. Furthermore, there is currently insufficient data to confirm the effectiveness of simethicone in relieving IPPUAD symptoms that occur within 30 minutes after a meal. IPPUAD is a symptom cluster characterized by flatulence, bloating, fullness, or pressure in the gastrointestinal tract, accompanied by upper abdominal discomfort, but without swallowing air or excessive stomach acid. For more complete data on the therapeutic uses of simethicone (11 types), please visit the HSDB record page. Drug Warnings…Simethicone used in combination with carbamazepine may cause carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to a patient who is taking carbamazepine. While there are currently no data on the use of simethicone in breastfeeding women, it is known that simethicone is not absorbed orally. Therefore, it does not enter breast milk. It is safe for breastfed infants to use. No special precautions are required. Simethicone appears to be non-toxic, and no adverse reactions have been reported. Pharmacodynamics: Simethicone reduces the surface tension of gas bubbles in the gastrointestinal tract, promoting their expulsion. Because it is usually taken as needed, its duration of action is short; and because it is not absorbed systemically, its therapeutic index is broad.

(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.)