Bismuth subsalicylate   中文名称: 碱式水杨酸铋

水杨酸和不溶性铋盐是在胃肠系统中由次水杨酸铋产生的。水杨酸抑制前列腺素 G/H 合酶 1/2，从而减轻胃和肠壁的炎症和刺激 [1]。次水杨酸铋（口服管饲；100 mg/kg-350 mg/kg）可降低小鼠粪便排出量（干重或湿重）和腹泻频率。当小鼠和大鼠接触蓖麻油时，它还能显着减少木炭测试餐沿着小肠的运输[2]。

Absorption, Distribution and Excretion
Following oral administration, bismuth subsalicylate is hydrolyzed in the stomach to bismuth and salicylic acid. Salicylic acid is almost completely absorbed in the small intestine, reaching peak plasma concentrations 1 to 2 hours after administration. In a study of healthy male subjects, after oral administration of 60 mL Pepto-Bismol (a common over-the-counter bismuth subsalicylate product, equivalent to 1050 mg of bismuth subsalicylate), the peak plasma concentration of salicylic acid was 40.1 μg/mL, with a time to peak concentration (Tmax) of 1.8 hours. Less than 1% of the bismuth subsalicylate is absorbed from the gastrointestinal tract into systemic circulation. In one study, after two weeks of oral administration of 787 mg bismuth subsalicylate chewable tablets, the mean glutar bismuth concentration was 5.1 ± 3.1 ng/mL. In another study, after oral administration of 525 mg bismuth subsalicylate liquid suspension, the mean glutar bismuth concentration ranged from 5 to 32 ng/mL.
After oral administration, the salicylate released from bismuth hyposalicylate is excreted in the urine. Bismuth is primarily excreted via urine and bile.
Currently, there is no relevant information.
The renal clearance of bismuth is 50 ± 18 mL/min.
The distribution of bismuth in autopsies of 22 patients who received therapeutic intramuscular injections (mainly bismuth salicylate) is as follows (median, mg/kg, wet weight): kidney 33.3; liver 6.8; spleen 1.6; colon 1.2; lung 0.9; brain 0.6; blood 0.5.
In the gastrointestinal tract, bismuth hyposalicylate is converted to salicylic acid and insoluble bismuth salts. A significant portion (over 90%) of the salicylate in bismuth hyposalicylate is absorbed and excreted in the urine. Bismuth hyposalicylate (bismuth salicylate) hydrolyzes in the gastrointestinal tract to bismuth salts and sodium salicylate. Two tablets or 30 mL of a suspension of this compound yield 204 mg and 258 mg of salicylate, respectively. Compared to organic bismuth compounds, inorganic bismuth salts have poorer water solubility and systemic absorption, but salicylates are still significantly absorbed. A brief study in 1992 found that 12 healthy subjects absorbed very little bismuth from bismuth hyposalicylate (serum concentrations were not specified), while one patient who took 216 mg of colloidal bismuth subcitrate experienced a peak serum bismuth concentration of 0.050 μg/ml. Studies have documented that some bismuth can be absorbed through the normal gastric mucosa, but the main absorption occurs in the duodenum.

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Metabolism/Metabolites
Bismuth hyposalicylate is hydrolyzed at pH less than 3. In the stomach, it is primarily hydrolyzed to bismuth oxychloride and salicylic acid. In the small intestine, unmetabolized bismuth hyposalicylate reacts with other anions (such as bicarbonate and phosphate) to form insoluble bismuth salts. In the colon, unmetabolized bismuth subsalicylate and other bismuth salts react with hydrogen sulfide produced by anaerobic bacteria to form bismuth sulfide, a highly insoluble black salt that causes dark stool color.
Biological Half-Life
After a single oral dose of 525 mg bismuth subsalicylate, the terminal half-life of salicylic acid is 2 to 5 hours. The intermediate half-life of bismuth is 5 to 11 days, and the terminal half-life is 21 to 72 days.

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Because infants may absorb salicylates through breast milk, alternative therapies are recommended.
◉ Effects on Breastfed Infants
There has been a case report of a 16-day-old breastfed infant developing metabolic acidosis after taking salicylates. The infant's mother was taking 650 mg of aspirin every 4 hours for arthritis. However, the case report did not test for salicylates in the mother's serum or breast milk, so it is unclear whether the infant directly ingested salicylates.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.
Protein Binding

The plasma protein binding rate of salicylic acid is approximately 90%. Bismuth has a plasma protein binding rate of over 90%.

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Interactions
When bismuth subsalicylate is taken concomitantly before or in a multiple-dose regimen with doxycycline, the bioavailability of doxycycline is significantly reduced by 37% and 51%, respectively. Bismuth subsalicylate should not be taken when doxycycline is used for therapeutic purposes.

[1]. Bismuth subsalicylate. Drug.bank.

[2]. Mucoadhesive effect of Curcuma longa extract and curcumin decreases the ranitidine effect, but not bismuth subsalicylate on ethanol-induced ulcer model. Sci Rep. 2019 Nov 12;9(1):16622.

Therapeutic Uses
Used as an intestinal absorbent. Veterinary Uses: Antidiarrheal. It has a weak intestinal disinfectant effect due to the release of salicylic acid. It is usually used in combination with carbonates to minimize the irritation of free acid while utilizing the protective effect of bismuth. CMPD is sometimes used orally to relieve diarrhea or soothe gastritis or peptic ulcers. Before the advent of penicillin, bismuth subsalicylate was widely used to treat syphilis…
/SRP: Formerly/Treatment of Vincent's pharyngitis, syphilis
For more complete data on the therapeutic uses of bismuth subsalicylate (7 types), please visit the HSDB records page. Drug Warnings Even in cases of widespread use, gradual intramuscular injection therapy for the treatment of syphilis rarely results in serious poisoning. Treatment is usually discontinued if gingivitis, proteinuria, rash, or significant diarrhea occurs.
When bismuth subsalicylate was taken concurrently with doxycycline or in a multi-dose regimen, the bioavailability of doxycycline was significantly reduced by 37% and 51%, respectively. Bismuth subsalicylate should not be taken while being treated with doxycycline. The authors advise travelers not to take these medications concurrently to prevent diarrhea.
Because bismuth is poorly absorbed in the systemic circulation, no significant amount of bismuth subsalicylate is expected to be excreted into breast milk. However, salicylates are excreted into breast milk, and are cleared from breast milk more slowly than from plasma, with the milk/plasma ratio increasing from 0.03–0.08 at 3 hours to 0.34 at 12 hours. Given the potential adverse effects on nursing infants, the American Academy of Pediatrics recommends caution when using salicylates during breastfeeding. A recent review also noted that bismuth subsalicylate should be avoided during breastfeeding due to systemic absorption of salicylates.
Although the toxicity risk may be small, prolonged exposure to salicylates can lead to serious adverse reactions in the fetus. Therefore, bismuth subsalicylate use during pregnancy should be limited to the first half of pregnancy, and the dosage should not exceed the recommended dose.

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Pharmacodynamics
Bismuth subsalicylate has antacid, antibacterial, gastroprotective, acid-suppressing, and anti-inflammatory effects. It can reduce the severity and incidence of flatulence and diarrhea, thereby relieving gastrointestinal discomfort. One study showed that bismuth subsalicylate has a prevention rate of over 60% against traveler's diarrhea. The organic bismuth compounds formed by the breakdown of bismuth subsalicylate in the gastrointestinal tract can inhibit the growth of Helicobacter pylori and other bacteria associated with gastrointestinal diseases, as well as certain fungi. One study showed that when bismuth subsalicylate is used as part of a quadruple therapy containing a proton pump inhibitor, tetracycline, and metronidazole, it can eradicate up to 90% of Helicobacter pylori infection. Bismuth subsalicylate also has antibacterial activity against Clostridium difficile, enterotoxigenic Escherichia coli O157:H7, norovirus, and other common intestinal pathogens such as Salmonella and Shigella.

C7H6BIO4

363.1005

361.999

14882-18-9

16682734

White to off-white solid powder

336.3ºC at 760mmHg

>35ºC

144.5ºC

4.45E-05mmHg at 25°C

0.974

55.76

1

4

0

12

173

0

QBWLKDFBINPHFT-UHFFFAOYSA-L

InChI=1S/C7H6O3.Bi.H2O/c8-6-4-2-1-3-5(6)7(9)10;;/h1-4,8H,(H,9,10);;1H2/q;+2;/p-2

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)

DMSO : ~1 mg/mL (~2.76 mM)
H2O : ~0.1 mg/mL (~0.28 mM)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。