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Famotidine (formerly YM-11170, MK208; MK-208, YM11170; Pepcid) is a competitive histamine H2–receptor antagonist with an IC50 of 0.6 mM. It is frequently used to treat heartburn, GERD, ulcers, and other digestive disorders because it inhibits the production of stomach acid. Famotidine does not appear to interact with other medications, unlike cimetidine, the first H2 antagonist, and it has no effect on the cytochrome P450 enzyme system.
Physicochemical Properties
| Molecular Formula | C8H15N7O2S3 | |
| Molecular Weight | 337.45 | |
| Exact Mass | 337.044 | |
| Elemental Analysis | C, 28.47; H, 4.48; N, 29.06; O, 9.48; S, 28.51 | |
| CAS # | 76824-35-6 | |
| Related CAS # | Famotidine-13C,d3; 2744683-81-4 | |
| PubChem CID | 5702160 | |
| Appearance | White to off-white solid powder | |
| Density | 1.8±0.1 g/cm3 | |
| Boiling Point | 662.4±65.0 °C at 760 mmHg | |
| Melting Point | 163-164°C | |
| Flash Point | 354.4±34.3 °C | |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C | |
| Index of Refraction | 1.808 | |
| LogP | -0.4 | |
| Hydrogen Bond Donor Count | 4 | |
| Hydrogen Bond Acceptor Count | 8 | |
| Rotatable Bond Count | 7 | |
| Heavy Atom Count | 20 | |
| Complexity | 469 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | S(C([H])([H])C1=C([H])SC(/N=C(\N([H])[H])/N([H])[H])=N1)C([H])([H])C([H])([H])/C(/N([H])[H])=N/S(N([H])[H])(=O)=O |
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| InChi Key | XUFQPHANEAPEMJ-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C8H15N7O2S3/c9-6(15-20(12,16)17)1-2-18-3-5-4-19-8(13-5)14-7(10)11/h4H,1-3H2,(H2,9,15)(H2,12,16,17)(H4,10,11,13,14) | |
| Chemical Name | 3-[[2-(diaminomethylideneamino)-1,3-thiazol-4-yl]methylsulfanyl]-N'-sulfamoylpropanimidamide | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | H2 receptor | ||
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Following oral administration, the absorption of famotidine is dose-dependent and incomplete. The oral bioavailability ranges from 40-50%, and the Cmax is reached in 1-4 hours post-dosing. While the bioavailability can be slightly increased with the intake of food and decreased by antacids, there is no clinical significance. About 65-70% of the total administered dose of famotidine undergoes renal elimination, and 30-35% of the dose is cleared by metabolism. Following intravenous administration, about 70% of the drug is eliminated in the urine as an unchanged drug. The steady-state volume of distribution ranges from 1.0 to 1.3 L/kg. Famotidine is found in breast milk; however, it is found in breast milk at the lowest concentrations compared to other H2 receptor antagonists. Renal clearance is 250-450 mL/min, indicating some tubular excretion. Because the renal clearance rate exceeds the glomerular filtration rate, famotidine is thought to be mainly eliminated via both glomerular filtration and renal tubular secretion. All H2-receptor antagonists are distributed in breast milk and cerebral spinal fluid. /Histamine H2-receptor antagonists/ Distribution of famotidine into human body tissues and fluids has not been fully characterized. The apparent volume of distribution of the drug is reported to be 1.1-1.4 l/kg in adults and does not appear to be altered substantially in patients with renal dysfunction. Following oral or IV administration in rats, famotidine is widely distributed, appearing in highest concentrations in the kidney, liver, pancreas, and submandibular gland. The drug is 15-20% protein bound. In rats famotidine appears to distribute only minimally into the CNS, and does not cross the placenta. It is not known whether the drug crosses the placenta in humans. Famotidine is distributed into milk in rats; however, it is not known whether the drug is distributed into milk in humans. Famotidine is excreted principally in urine via glomerular filtration and tubular secretion. Approximately 25-30 or 65-80% of a dose is excreted unchanged in urine within 24 hours following oral or IV administration, respectively, and approximately 13-49 or 52-82% of a single 40 mg oral or IV dose respectively, is excreted within 72 hours. ... The remainder of an orally administered dose is eliminated in feces. For more Absorption, Distribution and Excretion (Complete) data for FAMOTIDINE (7 total), please visit the HSDB record page. Metabolism / Metabolites Famotidine undergoes minimal first-pass metabolism. About 25-30% of the drug is eliminated through hepatic metabolism. The only metabolite identified in humans is the S-oxide. Famotidine is metabolized in the liver to famotidine S-oxide (S-famotidine). The metabolite does not appear to inhibit gastric acid secretion. Orally administered famotidine undergoes minimal metabolism on first pass through the liver. Biological Half-Life The elimination half-life is about 2 to 4 hours. The half-life is expected to increase nonlinearly in patients with decreased renal function. |
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| Toxicity/Toxicokinetics |
Interactions Concurrent use /of antacids/ with histamine H2-receptor antagonists in the treatment of peptic ulcer may be indicated for the relief of pain; however, simultaneous administration of antacids of medium to high potency (80 mmol to 150 mmol HCl) is not recommended since absorption of histamine H2-receptor antagonists may be decreased; patients should be advised not to take any antacids within 1/2 to 1 hour of histamine H2-receptor antagonists. /Histamine H2-receptor antagonists/ Concurrent use /of bone marrow depressants/ with H2-receptor antagonists may increase the risk of neutropenia or other blood dyscrasias. /Histamine H2-receptor antagonists/ Histamine H2-receptor antagonists may increase gastrointestinal pH; concurrent administration of ketoconazole with histamine H2-receptor antagonists may result in a marked reduction in absorption of ketoconazole; patients should be advised to take histamine H2-receptor antagonists at least 2 hours after ketoconazole. /Histamine H2-receptor antagonists/ Although a decrease in absorption is only reported in the literature for cimetidine and ranitidine, concurrent use with sucralfate may decrease the absorption of any H2-receptor antagonist; patients should be advised to take an H2-receptor antagonist 2 hours before sucralfate. /Histamine H2-receptor antagonists/ For more Interactions (Complete) data for FAMOTIDINE (10 total), please visit the HSDB record page. |
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| References |
[1]. Effects of the histamine H2 receptor antagonist famotidine on the healing of colonic anastomosis in rats. Clinics (Sao Paulo), 2009. 64(6): p. 567-70. [2]. Studies on the mechanism for the gastric mucosal protection by famotidine in rats. Jpn J Pharmacol, 1991. 55(2): p. 211-22. |
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| Additional Infomation |
Therapeutic Uses Anti-Ulcer Agents; Histamine H2 Antagonists Famotidine is currently the drug of choice for initial treatment and maintenance therapy in most patients with uncomplicated gastric or duodenal ulcer. ... A single bedtime dose of famotidine 40 mg is as efficatious as previously recommended multidose regimens and increases compliance. Histamine H2-receptor antagonists are indicated in the short-term treatment of active duodenal ulcer. They are also indicated (at reduce dosage) in the prevention of duodenal ulcer recurrence in selected patients. /Histamine H2-receptor antagonists; Included in US product labeling/ Famotidine ... /is/ indicated in the short-term treatment of active benign gastric ulcer. /Included in US product labeling/ For more Therapeutic Uses (Complete) data for FAMOTIDINE (12 total), please visit the HSDB record page. Drug Warnings Although appropriate studies on the relationship of age to the effects of these medicines /cimetidine, famotidine, and ranitidine/ have not been performed in the geriatric population, no geriatrics-specific problems have been documented to date. However, confusion is more likely to occur in elderly patients with impaired hepatic or renal function. Adverse nervous system effects (eg, headache, dizziness) and GI effects (eg, constipation, diarrhea) occur most frequently during famotidine therapy. Although adverse effects of the drug generally are not severe, discontinuance of famotidine therapy has been necessary in up to 14% of patients. Adverse effects generally are similar when famotidine is administered orally or IV. Fever, hypertension, flushing, musculoskeletal pain, arthralgia, and tinnitus have been reported in 1% or less of patients receiving famotidine, but a causal relationship to the drug has not been established in many cases. An acute episode of gout occurred in one patient during therapy with the drug. Leukocytosis, leukopenia, neutropenia, pancytopenia, agranulocytosis, eosinophilia, prolonged erythrocyte sedimentation rate (ESR), and thrombocytopenia have occurred rarely in patients receiving famotidine. Changes in serum protein or cholesterol concentrations also have occurred. For more Drug Warnings (Complete) data for FAMOTIDINE (10 total), please visit the HSDB record page. Pharmacodynamics Famotidine decreases the production of gastric acid, suppresses acid concentration and pepsin content, and decreases the volume of gastric secretion. Famotidine inhibits both basal and nocturnal gastric acid secretion, as well as acid secretion stimulated by food, caffeine, insulin, and pentagastrin. Famotidine has a dose-dependent therapeutic action, with the highest dose having the most extended duration of action and the highest inhibitory effect on gastric acid secretion. Following oral administration, the onset of action is within one hour, and the peak effect is reached within 1-3 hours. The duration of effect is about 10-12 hours. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.41 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.41 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.41 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9634 mL | 14.8170 mL | 29.6340 mL | |
| 5 mM | 0.5927 mL | 2.9634 mL | 5.9268 mL | |
| 10 mM | 0.2963 mL | 1.4817 mL | 2.9634 mL |