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Omeprazole

Basic information Uses Mechanisms of Action Drug Interactions Adverse reactions Preparation Safety Related Supplier
Omeprazole Basic information
Omeprazole Chemical Properties
  • Melting point:156°C
  • Boiling point:600.0±60.0 °C(Predicted)
  • Density 1.332 g/cm3
  • Flash point:9℃
  • storage temp. 2-8°C
  • solubility H2O: 0.5 mg/mL
  • pkapKa 4.14/8.9(H2O,t =25,I=0.025) (Uncertain)
  • form solid
  • color white
  • Water Solubility Soluble in water (0.5 mg/ml), DMSO (25 mg/ml), and ethanol (4.5 mg/ml).
  • Merck 14,6845
  • Stability:Stable, but hygroscopic and photosensitive. Incompatible with strong oxidizing agents. Store in the dark.
  • InChIKeySUBDBMMJDZJVOS-UHFFFAOYSA-N
  • CAS DataBase Reference73590-58-6(CAS DataBase Reference)
  • EPA Substance Registry System1H-Benzimidazole, 6-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]- (73590-58-6)
Safety Information
MSDS
Omeprazole Usage And Synthesis
  • UsesOmeprazole is a proton pump inhibitor used to treat diseases like gastroesophageal reflux disease (GERD), used for gastric and duodenal ulcers, reflux or erosive esophagitis, and Zollinger-Ellison syndrome. It is also effective for gastric and duodenal ulcers that are ineffective with H2 receptor antagonists. Injections of Omeprazole can also be used for: 1 gastrointestinal bleeding, such as peptic and anastomic ulcer bleeding, and the prevention of severe diseases (such as cerebral hemorrhage, severe trauma, etc.) and gastric surgery caused by upper intestinal bleeding; 2 acute gastric mucosal damage complicated by stress or nonsteroidal anti-inflammatory drugs; 3 general anesthesia, post-surgery, or coma patients, to prevent acid reflux and aspiration pneumonia; 4 Combined with amoxicillin and clarithromycin, or with metronidazole and clarithromycin, it can effectively kill Helicobacter pylori (Hp).
  • Mechanisms of ActionOmeprazole is a proton pump inhibitor which can specifically act on gastric parietal cell proton pump sites and transform into the active form of sulfonamide, then irreversibly binds to the proton pumps through disulfide bonds, generating a sulfonamide and proton pump compound (H + -K + -ATP), thereby inhibiting the enzymatic activity, preventing the H+ in parietal cells from being transported to the stomach cavity. It has a strong and persistent inhibitory role on gastric acid secretion caused by basal gastric acid and pentapeptide gastric acid secretions, greatly reducing gastric acid within the gastric juice. Rapid, reversible, and no H2 antagonist-induced psychiatric side effects.
  • Drug Interactions
    • Metronidazole and Hp-sensitive drugs (such as amoxicillin) acts in synergy with Omeprazole, improving the efficiency of Hp removal.
    • When combined with clarithromycin, the blood concentrations of both increase, increasing the incidence of adverse effects on the central nervous system and GI tract.
    • Omeprazole can improve the bioavailability of pancreatin, enhancing its efficacy. The two combined effectively treat obstructive diarrhea caused by cystic fibrosis of the pancreas and surgical diarrhea after extensive resection of the small intestine.
    • Combination with calcium antagonists slows down the clearance of both drugs, but without clinical significance.
    • Through CYP2C19 metabolism, extends the clearance of other enzymes such as diazepam, warfarin (R-warfarin), phenytoin, dicoumarol, nifedipine, antipyrine, and disulfiram in the liver. Omeprazole can lower acid, inhibiting activation of digoxin, reducing its efficacy. Digoxin dosages should be adjusted for a short period after discontinuation of use.
    • Combined with midazolam, lorazepam, or flurazepam, it can cause gait disorders, returning to normal after discontinuation of one drug.
    • Can inhibit the activation of prednisone, reducing its efficacy.
    • The acid suppression of Omeprazole can affect the absorption of iron salts.
    • Can reduce the absorption of Tetracycline, Ampicillin, Ketoconazole, and Iitraconazole, reducing blood plasma concentration, an effect related to the alkaline environment it causes.
    • Omeprazole inhibits the increase in gastric bacteria count from gastric acid, making nitrate carcinogenic; Combined with vitamins C or E, it may limit the formation of nitrous acid compounds.
    • No interaction with other antacids, but should not be combined.
    • Can influence blood plasma concentration of cyclosporine (positively or negatively), mechanism unknown.
    • No metabolic interaction with the following enzymes: caffeine, phenacetin, theophylline (CYP 1A2), S-warfarin, piroxicam, diclofenac and naproxen (CYP 2C9), lidocaine, quinidine, estradiol, erythromycin, budesonide (CYP 2D6), ethanol (CYP 2E1), lidocaine, quinidine, estradiol, erythromycin, and budesonide (CYP 3A).
  • Adverse reactionsOmeprazole is well tolerated, and most adverse reactions are mild and reversible.
    • Cardiovascular: chest pain, palpitations, tachycardia or bradycardia, elevated blood pressure, and peripheral edema.
    • Nervous: headaches, dizziness, weakness, paresthesia, depression, anxiety, apathy, confusion, drowsiness, hallucinations, agitation, insomnia, nervousness, aggressive behavior, tremors, and peripheral neuritis, etc.
    • Metabolism and secretion: rare excess sweating, hyponatremia, and gynecomastia. Long-term use can lead to vitamin B12 deficiency and gastrinemia.
    • Muscular: rare joint pain, muscle pain, and muscle weakness.
    • Genitourinary: microscopic pyuria, protonuria, hematuria, frequent urination, urinary tract infection, interstitial nephritis, glucose in urine, and testicular pain.
    • Gastrointestinal: dry mouth, sitiophobia, nausea, vomiting, acid reflux, abdominal distension, abdominal pain, diarrhea, constipation, etc. Rare stomatitis, taste disorders, and gastrointestinal candidiasis. Some patients reported significantly increased concentration of live gastric bacteria after taking Omeprazole for 14 days (returning to normal 3 days after discontinuation). There are reports of atrophic gastritis after long-term use.
    • Liver: rare hepatitis or icteric hepatitis, liver necrosis, liver failure, and hepatic encephalopathy. Occasional mild elevation of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and blood bilirubin was also observed.
    • Blood: hemolytic anemia was observed. Rare leukopenia, thrombocytopenia, agranulocytosis and various types of blood cell loss.
    • Skin: flush and dry skin. Rare dermatitis, pleomorphic erythema, Stevens-Johnson syndrome, toxic epithelial necrosis, and hair loss.
    • Allergic reactions: fever, rash, urticaria, itching, purpura, ecchymosis, angioneurotic edema, bronchospasm, and anaphylactic shock.
    • Eyes: rare blurred vision. One critically ill patient suffered from irreversible visual impairment after intravenous injection of Omeprazole at a high dosage.
    • 12 Other: Animal experiments show that Omeprazole can cause the proliferation of the main endocrine cells in the fundus and body of stomach (intestinal chromaffin cells). Long-term use can also cause gastric cancers.
  • Preparation
    • When used for intravenous drip, solvents or diluents except for 0.9% sodium chloride or 5% glucose are prohibited. Combination with other drugs is also prohibited.
    • Gastric ulcer patients should exclude the possibility of gastric cancer during usage, because it may alleviate symptoms, thereby delaying diagnosis.
    • Note post-treatment; do not discontinue usage because of symptom alleviation.
    • Large doses of Omeprazole should not be used in the long term (except for gastrinoma) to prevent excessive inhibition of acid.
    • Use 100 ml of a dedicated solvent after injection of 40 mg, with injection time of 2.5-4 min - solvent should be used within 2 hours after preparation. Alternatively, use a 100 ml diluted intravenous drip lasting 20-30 minutes or longer after 0.9% sodium chloride or 5% glucose injection.
    • Omeprazole does not affect driving or machine operation.
    • Use with caution in the case of liver or renal dysfunction.
    • FDA pregnancy safety category C.
  • DescriptionOmeprazole is a potent gastric antisecretory agent with selective inhibitory effect on the H+,K+-ATPase proton pump. It is highly effective in the treatment of duodenal ulcer and Zollinger-Ellison syndrome, and is reportedly superior to ranitidine in the management of reflux esophagitis.
  • Chemical PropertiesWhite Crystalline Solid
  • OriginatorAstra (Sweden)
  • UsesBinds covalently to proton pump. It inhibits gastric secretion. Used as an anttiulcerative
  • Usesdiuretic, sweetener, diagnostic aid
  • UsesA selective proton pump and CYP inhibitor
  • UsesOmeprazole Pellets are used in the treatment of Gastroesophageal reflux disease (GERD): A condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus)
  • DefinitionChEBI: A member of the class of benzimidazoles that is 1H-benzimidazole which is substituted by a [4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl group at position 2 and a methoxy group at position 5.
  • Manufacturing Process3,5-Lutidine-N-Oxide Hydrogen peroxide (45%, 200 ml) was added dropwise at 60°-70°C during 2 hours to a mixture of 3,5-Lutidine (125 g, 1.16 mole) and acetic acid (400 ml). The mixture was heated to 90°C and maintained at 90°-100°C for 2 hours after which it was cooled to 60°C. Again hydrogen peroxide (45%, 200 ml) was added dropwise at 60°-70°C during 1 hour and then the mixture was heated to 90°C and maintained at 90°-100°C for 6 hours. Thereafter, acetic acid and water was distilled off under reduced pressure and the distillation residue obtained was used as a starting product for the nitration.
    3,5-Dimethyl-4-nitropyridine-N-oxide To the distillation above obtained residue was added sulphuric acid (146 ml). Thereafter, a nitrating mixture consisting of sulphuric acid (250 ml) and nitric acid (280 ml) was added dropwise during 4 hours at 90°-100°C. The reactionmixture was heated further at 90°-100°C for 6 hours, after which it was cooled and poured over crushed ice (4 kg), Caustic lye (50%, 1150 ml) was added to the yellow solution and the precipitated crystalline compound was filtered under suction. The cake was washed with water and dried in vacuuo oven to yield the product which melted at 171°-173°C. Yield 78.5%. A sample crystallized from acetone had a melting point of 174°-174.5°C.
    3,5-Dimethyl-4-nitropyridine-N-oxide-dimethyl sulfate adduct To a suspension of 3,5-dimethyl-4-nitropyridine-N-oxide (150 g, 0.80 mole) in acetone (450 ml) was added dimethyl sulfate (90 ml, 0.95 mole). The mixture was heated to reflux until a clear solution was obtained and then allowed to cool to ambient temperature. An off-white crystalline solid separated out, which was filtered, washed with acetone and dried to yield 220 g of the adduct. Yield was 83.8% of theoretical.
    3,5-Dimethyl-2-hydroxymethyl-4-nitropyridine 3,5-Dimethyl-4-nitropyridine-N-oxide-dimethyl sulfate adduct (220 g, 0.75 mole) was dissolved in methanol (1.0 ltr) and the solution heated to reflux. A solution of ammonium persulfate (140 gm) in water (200 ml) was added dropwise over 4 hours after which reflux was continued for 4 hours. Methanol was distilled off under reduced pressure and the residue was basified to pH 10 by addition of caustic lye (105 ml). The mixture was extracted with dichloromethane (2 times 400 ml). The dichloromethane layer was dried over sodium sulfate and filtered. The product was used as its solution in dichloromethane for the next reaction.
    2-Chloromethyl-3,5-dimethyl-4-nitropyridine hydrochloride To the cooled dichloromethane solution of 3,5-dimethyl-2-hydroxymethyl-4nitropyridine was added thionyl chloride (60 ml, 0.85 mole) dropwise over a period of 2 hours and stirring was continued for a further 2 hours. Methanol (10 ml) was added to destroy excess thionyl chloride and separated product was filtered under suction and washed with dichloromethane. The cake was dried in vacuum oven to yield 55 g of a cream colored product. Melting point was 124°-126°C.
    5-Methoxy-2-[(3,5-dimethyl-4-nitro-2-pyridinyl)methylthio]-1H-benzimidazole To a suspension of 5-methyl-2-mercaptobenzimidazole (36 g, 0.2 mole), 2chloromethyl-3,5-dimethyl-4-nitropyridine hydrochloride (47.4 g, 0.2 mole) and triethyl benzylammonium chloride (5 g) in a dichloromethane (500 ml) was added dropwise a solution of NaOH (17.6 gm, 0.44 mole) in water (30 ml). The addition was exothermic and the temperature was observed to rise to 40°C with reflux of dichloromethane - the reaction mixture was stirred for further 6 hours at ambient temperature and filtered. The cake was washed with water and dried in vacuum oven to yield 55.8 g of cream color product. Yield 81.1%; melting point 124°-128°C.
    5-Methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridinyl)methylthio]-1Hbenzimidazole
    5-Methoxy-2-[(3,5-dimethyl-4-nitro-2-pyridinyl)methylthio]-1Hbenzimidazole(50 g, 0.145 mole) was dissolved in methanol and heated to 45°C. A solution of sodium methoxide (50 g, 0.925 mole) in methanol (150 ml) was added dropwise over a period of 3 hours at 45°-60°C. Stirring was continued for another 2 hours and then methanol was distilled off under reduced pressure. To the cooled residue was added water (200 ml) followed by concentrated HCl (65 ml) until the pH of the mixture was 7.5. The reaction mixture was extracted with dichloromethane and the dichloromethane layer was washed with water (2 times 100 ml). The dichloromethane layer was dried over sodium sulfate and concentrated to yield the product as an amber color syrup. Yield was 40.1 gm, about 83.8% of theoretical. A solid sample was obtained by trituration of the syrup several times with petroleum ether. Melting point was 87°-90°C.
    5-Methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridinyl)methylthio]-1Hbenzimidazolehydrochloride HCl gas was bubbled into a cooled solution of 5-methoxy-2-[(3,5-dimethyl-4methoxy-2-pyridinyl)methylthiol]-1H-benzimidazole (50 g) in dichloromethane (250 ml) until no more precipitation was observed. The reaction mixture was warmed to 40°C and again cooled to 10°C. The solid was filtered under suction and washed with dichloromethane to yield the product (49 g) as a cream colored fine granular solid. Yield was 88.2% of theoretical. Melting point 144°-148°C.
    Omeprazole from 5-methoxy-2-[(3,5-dimethyl-4-methoxy-2pyridinyl)methylthiol]-1H-benzimidazole To a solution of 5-methoxy-2-[(3,5-dimethyl-4-methoxy-2pyridinyl)methylthio]-1H-benzimidazole (32.9 g, 0.1 mole) in dichloromethane (200 ml) was added phthalic anhydride (20 g, 0.135 mole) and cooled in an ice salt bath. This was followed by addition of sodium carbonate (18 g, 0.17 mole) and water (20 ml). Hydrogen peroxide (12 ml, 45%, 0.16 mm mole) was added dropwise at -5°-0°C and the reaction mixture was stirred at the same temperature. When the reaction was complete as indicated by TLC, water (200 ml) was added, cooling bath was removed and the reaction mixture was stirred for 10 mins. The organic layer was separated and washed with 5% sodium carbonate solution. The separated dichloromethane solution was charcoalised and filtered through celite. The filtrate was concentrated to 100 ml and ethyl acetate 100 ml was added thereto. The separated solid was filtered, washed with ethyl acetate and dried in vacuum oven to yield 28.20 g of omeprazole. Yield 82.4% of theoretical. Melting point was 158°-160°C (dec.).
  • brand name. Prilosec (AstraZeneca).
  • Therapeutic FunctionAntiulcer
  • World Health Organization (WHO)Omeprazole was introduced in the 1980s. It belongs to a group of agents that have an inhibitory effect on the secretion of hydrochloric acid in the stomach (gastric acid proton pump inhibitors) and is used in the treatment of upper gastrointestinal tract disorders. The Committee for Proprietary Medicinal Products of the European Commission has concluded that a causal association between the reactions reported in Germany and the use of omeprazole had not been established. Nevertheless oral administration should be preferred. (Reference: (CPMPPO) Pharmacovigilance Opinion, No.16 , , 25 July 1994)
  • General DescriptionOmeprazole, 5-methoxy-2-(((4-methoxy-3, 5-dimethyl-2-pyridinyl)methyl) sulfinyl)-1Hbenzimidazole(Losec), is a white to off-white crystallinepowder with very slight solubility in water. Omeprazole isan amphoteric compound (pyridine N, pKa 4.06; benzimidazoleN-H, pKa 0.79), and consistent with the proposedmechanism of action of the substituted benzimidazoles, isacid labile. Hence, the omeprazole product is formulatedas delayed-release capsules containing enteric-coatedgranules.
    The absolute bioavailability of orally administeredorneprazole is 30% to 40% related to substantial first-passbiotransformation. The drug has a plasmahalf-life of about 1 hour. Most (77%) of an oral dose ofomeprazole is excreted in the urine as metabolites with insignificantantisecretory activity. The primary metabolitesof omeprazole are 5-hydroxyomeprazole (CYP2C19) andomeprazole sulfone (CYP3A4). The antisecretory actions ofomeprazole persist for 24 to 72 hours, long after the drughas disappeared from plasma, which is consistent with itssuggested mechanism of action involving irreversible inhibitionof the proton pump.
    Omeprazole is approved for the treatment of heartburn,GERD, duodenal ulcer, erosive esophagitis, gastric ulcer,and pathological hypersecretory conditions.
  • Biological ActivityH + ,K + -ATPase inhibitor (IC 50 = 5.8 μ M) that displays antisecretory and antiulcer activity. Inhibits gastric acid secretion (IC 50 = 0.16 μ M for histamine-induced acid formation) and reduces gastric lesion formation induced by a variety of ulcerative stimuli. Antibacteral against Helicobacter pylori in vitro . Also inhibits CYP2C19, CYP2C9 and CYP3A (K i values are 3.1, 40.1 and 84.4 μ M respectively) and blocks swelling-dependent chloride channels (ICIswell).
  • Veterinary Drugs and TreatmentsOmeprazole is potentially useful in treating both gastroduodenal ulcer disease and to prevent or treat gastric erosions caused by ulcerogenic drugs (e.g., aspirin). An oral paste product is labeled for the treatment and prevention of recurrence of gastric ulcers in horses.
  • Metabolic pathwayWhen male humans are given 14C-omeprazole orally, an average of 79% of the dose is recovered in the urine in 96 h. Omeprazole is completely metabolized and at least six metabolites are identified. Two major metabolites are hydroxyomeprazole and omeprazole acid.
Omeprazole Preparation Products And Raw materials
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