Peringatan Keamanan

Lowest Lethal Dose (LDLo) in humans is 700 mg/kg. LD50 in rats is 1200 mg/kg via oral route, 542 mg/kg via intraperitoneal route, and 980 mg/kg via subcutaneous route.L32338

Overdose of bismuth subsalicylate over an extended period of time and consequently, bismuth toxicity, can lead to blackening of the tongue and teeth, fatigue, mood changes, deterioration of mental status, and neurotoxicity. Other signs and symptoms include impaired cognition, tremors, lethargy, somnolence, insomnia, delirium, myoclonus, seizures, depressed mood, anxiety, and a depressed mood.A230728 Salicylate toxicity can occur from chronic bismuth subsalicylate use A230978: it mostly occurs from ingestion of more than 150 mg/kg of salicylates (or >6.5 g of aspirin equivalent).A230728 As there are no specific antidotes for bismuth salicylate toxicity, overdose should be managed with supportive care, with or without decontamination with activated charcoal. Hemodialysis may be considered in more severe cases and with the presence of altered mental status and metabolic acidosis.A230728

Bismuth subsalicylate

DB01294

small molecule approved vet_approved

Deskripsi

Bismuth subsalicylate is an antacid and anti-diarrheal agent. Exhibiting antibacterial and gastroprotective properties, bismuth subsalicylate is an insoluble salt of salicylic acid linked to trivalent bismuth cation. Each molecule of bismuth subsalicylate contains 58% bismuth and 42% salicylate by weight.A230733 Bismuth subsalicylate has been around for over 100 years: it was originally developed in 1901 for hygienic use and sanitation for cholera infection.A230728, A230773

Bismuth subsalicylate was first approved by the FDA in 1939 and is now mainly used to relieve nausea, diarrhea, and gastrointestinal discomfort.A230728 It is an active ingredient found in Pepto-Bismol, a common over-the-counter medication that is used to temporarily treat discomforts of the stomach and gastrointestinal tract.L32318 Bismuth subsalicylate is a component of HELIDAC Therapy (bismuth subsalicylate, metronidazole, and tetracycline), which is a treatment regimen indicated for the eradication of H. pylori for treatment of patients with H. pylori infection and duodenal ulcer disease.L32363

Struktur Molekul 2D

Berat 362.0926
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal half-life of salicylic acid following a single oral dose of 525 mg bismuth subsalicylate is ranges from two to five hours. Bismuth has an intermediate half-life of 5 to 11 days and a terminal half-life of 21 to 72 days.[L32363]
Volume Distribusi There is no information available.
Klirens (Clearance) The renal clearance of bismuth is 50 ± 18 mL/min.[L32363]

Absorpsi

Following oral administration, bismuth subsalicylate hydrolyzes into bismuth and salicylic acid in the stomach. Salicylic acid is almost completely absorbed in the small intestine and reaches plasma peak levels one to two hours after dosing. In one study involving healthy male subjects, oral administration of 60 mL Pepto-Bismol, a common over-the-counter product of bismuth subsalicylate, equivalent to 1050 mg of bismuth subsalicylate, resulted in the peak plasma concentration of salicylate of 40.1 ?g/mL, with a time to peak concentration (Tmax) of 1.8 hours.A230733 Less than 1% of bismuth from bismuth subsalicylate is absorbed from the gastrointestinal tract into the systemic circulation. In one study, oral administration of 787 mg bismuth subsalicylate in the chewable tablet form for two weeks resulted in the mean trough blood bismuth concentration was 5.1 ± 3.1 ng/mL. In another study, the mean trough blood bismuth concentration ranged from five to 32 ng/mL following oral administration of 525 mg bismuth subsalicylate in the liquid suspension form.L32363

Metabolisme

Bismuth subsalicylate undergo hydrolysis at pH levels lesser than three. It is largely hydrolyzed in the stomach to bismuth oxychloride and salicylic acid. In the small intestine, unchanged bismuth subsalicylate reacts with other anions such as bicarbonate and phosphate to form insoluble bismuth salts. In the colon, unchanged bismuth subsalicylate and other bismuth salts react with hydrogen sulfide produced by anaerobic bacteria to form bismuth sulfide, a highly insoluble black salt responsible for the darkening of the stools.A230733

Rute Eliminasi

Following oral administration, salicylate dissociated from bismuth subsalicylate is excreted in the urine.A230733 Bismuth is primarily eliminated via urinary and biliary routes.L32363

Interaksi Obat

384 Data
Ammonium chloride The serum concentration of Bismuth subsalicylate can be increased when it is combined with Ammonium chloride.
Ginkgo biloba The risk or severity of bleeding can be increased when Ginkgo biloba is combined with Bismuth subsalicylate.
Methotrexate The serum concentration of Methotrexate can be increased when it is combined with Bismuth subsalicylate.
Pralatrexate The serum concentration of Pralatrexate can be increased when it is combined with Bismuth subsalicylate.
Probenecid The therapeutic efficacy of Probenecid can be decreased when used in combination with Bismuth subsalicylate.
Treprostinil The risk or severity of bleeding can be increased when Treprostinil is combined with Bismuth subsalicylate.
Doxycycline The serum concentration of Doxycycline can be decreased when it is combined with Bismuth subsalicylate.
Lymecycline The serum concentration of Lymecycline can be decreased when it is combined with Bismuth subsalicylate.
Clomocycline The serum concentration of Clomocycline can be decreased when it is combined with Bismuth subsalicylate.
Oxytetracycline The serum concentration of Oxytetracycline can be decreased when it is combined with Bismuth subsalicylate.
Demeclocycline The serum concentration of Demeclocycline can be decreased when it is combined with Bismuth subsalicylate.
Tetracycline The serum concentration of Tetracycline can be decreased when it is combined with Bismuth subsalicylate.
Metacycline The serum concentration of Metacycline can be decreased when it is combined with Bismuth subsalicylate.
Minocycline The serum concentration of Minocycline can be decreased when it is combined with Bismuth subsalicylate.
Sarecycline The serum concentration of Sarecycline can be decreased when it is combined with Bismuth subsalicylate.
Omadacycline The serum concentration of Omadacycline can be decreased when it is combined with Bismuth subsalicylate.
Penimepicycline The serum concentration of Penimepicycline can be decreased when it is combined with Bismuth subsalicylate.
Ketoprofen The risk or severity of bleeding and gastrointestinal bleeding can be increased when Bismuth subsalicylate is combined with Ketoprofen.
Dexketoprofen The risk or severity of bleeding and gastrointestinal bleeding can be increased when Bismuth subsalicylate is combined with Dexketoprofen.
Dicoumarol Bismuth subsalicylate may increase the anticoagulant activities of Dicoumarol.
Phenindione Bismuth subsalicylate may increase the anticoagulant activities of Phenindione.
Warfarin Bismuth subsalicylate may increase the anticoagulant activities of Warfarin.
Phenprocoumon Bismuth subsalicylate may increase the anticoagulant activities of Phenprocoumon.
Acenocoumarol Bismuth subsalicylate may increase the anticoagulant activities of Acenocoumarol.
4-hydroxycoumarin Bismuth subsalicylate may increase the anticoagulant activities of 4-hydroxycoumarin.
Coumarin Bismuth subsalicylate may increase the anticoagulant activities of Coumarin.
(R)-warfarin Bismuth subsalicylate may increase the anticoagulant activities of (R)-warfarin.
Ethyl biscoumacetate Bismuth subsalicylate may increase the anticoagulant activities of Ethyl biscoumacetate.
Fluindione Bismuth subsalicylate may increase the anticoagulant activities of Fluindione.
Clorindione Bismuth subsalicylate may increase the anticoagulant activities of Clorindione.
Diphenadione Bismuth subsalicylate may increase the anticoagulant activities of Diphenadione.
Tioclomarol Bismuth subsalicylate may increase the anticoagulant activities of Tioclomarol.
(S)-Warfarin Bismuth subsalicylate may increase the anticoagulant activities of (S)-Warfarin.
Digoxin The serum concentration of Digoxin can be decreased when it is combined with Bismuth subsalicylate.
Acetyldigitoxin The serum concentration of Acetyldigitoxin can be decreased when it is combined with Bismuth subsalicylate.
Deslanoside The serum concentration of Deslanoside can be decreased when it is combined with Bismuth subsalicylate.
Ouabain The serum concentration of Ouabain can be decreased when it is combined with Bismuth subsalicylate.
Digitoxin The serum concentration of Digitoxin can be decreased when it is combined with Bismuth subsalicylate.
Oleandrin The serum concentration of Oleandrin can be decreased when it is combined with Bismuth subsalicylate.
Cymarin The serum concentration of Cymarin can be decreased when it is combined with Bismuth subsalicylate.
Proscillaridin The serum concentration of Proscillaridin can be decreased when it is combined with Bismuth subsalicylate.
Metildigoxin The serum concentration of Metildigoxin can be decreased when it is combined with Bismuth subsalicylate.
Lanatoside C The serum concentration of Lanatoside C can be decreased when it is combined with Bismuth subsalicylate.
Gitoformate The serum concentration of Gitoformate can be decreased when it is combined with Bismuth subsalicylate.
Acetyldigoxin The serum concentration of Acetyldigoxin can be decreased when it is combined with Bismuth subsalicylate.
Peruvoside The serum concentration of Peruvoside can be decreased when it is combined with Bismuth subsalicylate.
Tioguanine The metabolism of Tioguanine can be decreased when combined with Bismuth subsalicylate.
Azathioprine The metabolism of Azathioprine can be decreased when combined with Bismuth subsalicylate.
Mercaptopurine The metabolism of Mercaptopurine can be decreased when combined with Bismuth subsalicylate.
Bismuth subcitrate potassium Bismuth subsalicylate may increase the neurotoxic activities of Bismuth subcitrate potassium.
Bismuth subcarbonate Bismuth subsalicylate may increase the neurotoxic activities of Bismuth subcarbonate.
Bismuth subnitrate Bismuth subsalicylate may increase the neurotoxic activities of Bismuth subnitrate.
Bismuth subgallate Bismuth subsalicylate may increase the neurotoxic activities of Bismuth subgallate.
Valproate bismuth Bismuth subsalicylate may increase the neurotoxic activities of Valproate bismuth.
Lepirudin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Lepirudin.
Bivalirudin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Bivalirudin.
Alteplase The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Alteplase.
Urokinase The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Urokinase.
Reteplase The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Reteplase.
Anistreplase The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Anistreplase.
Tenecteplase The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Tenecteplase.
Abciximab The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Abciximab.
Drotrecogin alfa The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Drotrecogin alfa.
Streptokinase The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Streptokinase.
Argatroban The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Argatroban.
Ardeparin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Ardeparin.
Fondaparinux The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Fondaparinux.
Pentosan polysulfate The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Pentosan polysulfate.
Dipyridamole The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Dipyridamole.
Heparin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Heparin.
Enoxaparin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Enoxaparin.
Epoprostenol The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Epoprostenol.
Ximelagatran The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Ximelagatran.
Desmoteplase The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Desmoteplase.
Defibrotide The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Defibrotide.
Ancrod The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Ancrod.
Beraprost The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Beraprost.
Prasugrel The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Prasugrel.
Rivaroxaban The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Rivaroxaban.
Sulodexide The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Sulodexide.
Semuloparin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Semuloparin.
Idraparinux The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Idraparinux.
Cangrelor The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Cangrelor.
Astaxanthin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Astaxanthin.
Apixaban The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Apixaban.
Otamixaban The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Otamixaban.
Amediplase The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Amediplase.
Dabigatran etexilate The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Dabigatran etexilate.
Danaparoid The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Danaparoid.
Dalteparin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Dalteparin.
Tinzaparin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Tinzaparin.
Nadroparin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Nadroparin.
Triflusal The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Triflusal.
Ticagrelor The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Ticagrelor.
Ditazole The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Ditazole.
Vorapaxar The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Vorapaxar.
Edoxaban The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Edoxaban.
Sodium citrate The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Sodium citrate.
Dextran The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Dextran.
Bemiparin The risk or severity of bleeding can be increased when Bismuth subsalicylate is combined with Bemiparin.

Referensi & Sumber

Synthesis reference: Richard William Hess, "Pigmentary bright primrose yellow monoclinic bismuth vanadate and processes for the preparation thereof." U.S. Patent US4115142, issued December, 1925.
Artikel (PubMed)
  • PMID: 1158081
    Goldenberg MM, Honkomp LJ, Burrous SE, Castellion AW: Protective effect of Pepto-Bismol liquid on the gastric mucosa of rats. Gastroenterology. 1975 Sep;69(3):636-40.
  • PMID: 32809532
    Budisak P, Patel P, Abbas M: Bismuth Subsalicylate .
  • PMID: 2406853
    Bierer DW: Bismuth subsalicylate: history, chemistry, and safety. Rev Infect Dis. 1990 Jan-Feb;12 Suppl 1:S3-8. doi: 10.1093/clinids/12.supplement_1.s3.
  • PMID: 3308391
    DuPont HL: Bismuth subsalicylate in the treatment and prevention of diarrheal disease. Drug Intell Clin Pharm. 1987 Sep;21(9):687-93. doi: 10.1177/106002808702100901.
  • PMID: 15691943
    Dodge AG, Wackett LP: Metabolism of bismuth subsalicylate and intracellular accumulation of bismuth by Fusarium sp. strain BI. Appl Environ Microbiol. 2005 Feb;71(2):876-82. doi: 10.1128/AEM.71.2.876-882.2005.
  • PMID: 9354203
    Graham DY, Hoffman J, el-Zimaity HM, Graham DP, Osato M: Twice a day quadruple therapy (bismuth subsalicylate, tetracycline, metronidazole plus lansoprazole) for treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 1997 Oct;11(5):935-8. doi: 10.1046/j.1365-2036.1997.00219.x.
  • PMID: 25251194
    Keogan DM, Griffith DM: Current and potential applications of bismuth-based drugs. Molecules. 2014 Sep 23;19(9):15258-97. doi: 10.3390/molecules190915258.
  • PMID: 25901890
    Pitz AM, Park GW, Lee D, Boissy YL, Vinje J: Antimicrobial activity of bismuth subsalicylate on Clostridium difficile, Escherichia coli O157:H7, norovirus, and other common enteric pathogens. Gut Microbes. 2015;6(2):93-100. doi: 10.1080/19490976.2015.1008336.
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