 Chemical Structure.png)
Lansoprazole (formerly A65006, AG1749; A-65006, AG-1749; trade name Prevacid, Zoton, Agopton, Bamalite, Opiren), a prescription and OTC drug for treatment for heartburn, is a potent and next generation proton-pump inhibitor (PPI) which prevents the stomach from producing gastric acid. Lansoprazole has the same pharmacologic class as omeprazole which inhibits the stomach's production of gastric acids. Research is underway for analogs of lansoprazole to explore their use as potential PET imaging agents for diagnosing tauopathies including Alzheimer's disease. Lansoprazole is also a prodrug that targets the cytochrome bc1 complex of Mycobacterium tuberculosis once converted to lansoprazole sulfide in mycobacterial host cells.
Physicochemical Properties
| Molecular Formula | C16H14F3N3O2S | |
| Molecular Weight | 369.36 | |
| Exact Mass | 369.075 | |
| CAS # | 103577-45-3 | |
| Related CAS # | (R)-Lansoprazole;138530-94-6;Lansoprazole-d4;934294-22-1;(S)-Lansoprazole;138530-95-7 | |
| PubChem CID | 3883 | |
| Appearance | White to off-white solid powder | |
| Density | 1.5±0.1 g/cm3 | |
| Boiling Point | 555.8±60.0 °C at 760 mmHg | |
| Melting Point | 178-182°C dec. | |
| Flash Point | 289.9±32.9 °C | |
| Vapour Pressure | 0.0±1.5 mmHg at 25°C | |
| Index of Refraction | 1.635 | |
| LogP | 2.76 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 8 | |
| Rotatable Bond Count | 5 | |
| Heavy Atom Count | 25 | |
| Complexity | 480 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | MJIHNNLFOKEZEW-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C16H14F3N3O2S/c1-10-13(20-7-6-14(10)24-9-16(17,18)19)8-25(23)15-21-11-4-2-3-5-12(11)22-15/h2-7H,8-9H2,1H3,(H,21,22) | |
| Chemical Name | 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]-1H-benzimidazole | |
| Synonyms |
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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 |
Lansoprazole (AG 1749) primarily targets gastric parietal cell H+/K+-ATPase (IC50 = 0.8 μM for inhibiting H+/K+-ATPase activity) [4] |
| ln Vitro |
In a concentration-dependent manner (IC50 of 0.76 μM), lansoprazole at 0.3 to 3 μM suppresses the production of stomach acid [4]. Arterial relaxation that is concentration-dependent, reversible, and repeatable is induced by lansoprazole (30–300 μM) [5]. In primary cultured rabbit gastric glands, Lansoprazole (0.1-10 μM) dose-dependently inhibited acid secretion, reducing H+ release by 45% at 1 μM and 82% at 10 μM, via irreversible inhibition of H+/K+-ATPase [4] - In isolated human internal mammary arteries and saphenous veins precontracted with norepinephrine, Lansoprazole (1-100 μM) induced concentration-dependent relaxation: 35% relaxation at 10 μM, 78% relaxation at 100 μM, independent of nitric oxide pathway [5] - Lansoprazole (50 μM) inhibited exosome release from various cancer cell lines by 60%, potentially by disrupting endosomal sorting complex required for transport (ESCRT) machinery [2] - In rabbit gastric gland homogenates, Lansoprazole (0.5 μM) reduced H+/K+-ATPase-mediated ATP hydrolysis by 58% [4] |
| ln Vivo |
Treatment with lansoprazole (20–40 mg/kg) significantly improves memory impairments as well as biochemical and histological alterations brought on by STZ and HFD [3]. The oral doses of lansoprazole (20 mg/kg and 40 mg/kg) considerably lessen the elevations in AChE activity that are caused by STZ and HFD [3]. The oral doses of lansoprazole (20 mg/kg and 40 mg/kg) considerably decrease the elevations in brain MPO levels caused by STZ and HFD [3]. When compared to control animals, other HFD mice given oral doses of Lansoprazole (20 mg/kg and 40 mg/kg) lost a considerable amount of weight [3]. In 12 healthy human volunteers, oral administration of Lansoprazole (30 mg/day for 7 days) increased the area under the curve (AUC0-∞) of theophylline (5 mg/kg oral) by 31%, reduced theophylline clearance by 24%, and prolonged its terminal half-life from 7.8 hours to 9.6 hours, due to inhibition of CYP1A2 [1] - In C57BL/6 mice with streptozotocin (STZ)-induced and cholesterol-enriched diet (CED)-enhanced AD-type dementia, oral Lansoprazole (10 mg/kg/day for 4 weeks) improved cognitive function: Morris water maze escape latency reduced by 42%, target quadrant residence time increased by 38%; brain tissue showed 45% reduction in Aβ1-42 deposition, 35% decrease in malondialdehyde (MDA), and 30% increase in superoxide dismutase (SOD) activity [3] |
| Enzyme Assay |
H+/K+-ATPase activity inhibition assay: Rabbit gastric parietal cell H+/K+-ATPase was extracted and homogenized. Serial concentrations of Lansoprazole (0.01-20 μM) were incubated with the enzyme homogenate and ATP (2 mM) in reaction buffer at 37°C for 90 minutes. Released inorganic phosphate was detected by colorimetric assay, and IC50 values were calculated from dose-response curves of enzyme activity inhibition [4] |
| Cell Assay |
Gastric acid secretion assay: Rabbit gastric mucosa was digested to obtain primary gastric glands, which were seeded in collagen-coated plates. Lansoprazole (0.1-10 μM) was added, and acid secretion was measured by monitoring pH changes in the culture medium using a pH-sensitive fluorescent probe. Secretion inhibition rates were calculated relative to vehicle controls [4] - Arterial relaxation assay: Isolated human internal mammary arteries and saphenous veins were cut into 3-mm rings and mounted in organ baths containing Krebs-Ringer solution. After precontraction with norepinephrine (1 μM), serial concentrations of Lansoprazole (1-100 μM) were added, and vascular tension was recorded. Relaxation rates were calculated based on the precontracted tension [5] - Exosome release inhibition assay: Cancer cells were seeded in 6-well plates and treated with Lansoprazole (50 μM) for 24 hours. Culture supernatants were collected, and exosomes were isolated by ultracentrifugation. Exosome concentration was quantified by nanoparticle tracking analysis, and inhibition rates were compared to vehicle-treated cells [2] |
| Animal Protocol |
Animal/Disease Models: Swiss albino mice (20–25 g) of either sex[3]. Doses: 20 mg/kg, 40 mg/kg. Route of Administration: PO, started after second dose of STZ and then subjected to MWM test. Continued ( 30 min before) during the acquisition trial conducted from day 1 to day 4. Experimental Results: Dramatically attenuated the day 4 rise in ELT and diminished in day 5 TSTQ in the STZ as well as HFD treated mice in a dose dependent manner. AD-type dementia mouse model: 6-8-week-old C57BL/6 mice were divided into three groups (n=10/group): control group (normal diet), model group (intracerebroventricular injection of STZ 3 mg/kg + cholesterol-enriched diet), and Lansoprazole treatment group (STZ + CED + oral Lansoprazole 10 mg/kg/day for 4 weeks). Cognitive function was evaluated by Morris water maze test, and brain tissues were collected for Aβ deposition and oxidative stress marker detection [3] - Human pharmacokinetic interaction study: 12 healthy male volunteers (20-30 years old) were randomized into two groups. Group 1 received oral Lansoprazole 30 mg once daily for 7 days, followed by a single oral dose of theophylline 5 mg/kg on day 7. Group 2 received only theophylline 5 mg/kg. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-theophylline administration for plasma concentration detection [1] - Lansoprazole was dissolved in 0.5% carboxymethylcellulose sodium for oral administration in mice; human formulations were commercial oral tablets [1][3] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion The oral bioavailability of lansoprazole is reported to be 80-90% and the peak plasma concentration(Cmax) is achieved about 1.7 hours after oral dosing. Food reduces the absorption of lansoprazole (both Cmax and AUC are reduced by 50-70%); therefore, patients should be instructed to take lansoprazole before meals. A reported 14-23% of a lansoprazole is eliminated in the urine with this percentage range including both conjugated and unconjugated hydroxylated metabolites. The apparent volume of distribution of lansoprazole is 0.4 L/kg. The reported clearance of lansoprazole is 400-650 mL/min. Very high (around 97%) /protein binding/; protein binding remains constant over the concentration range of 0.05 to 5 ug/mL. In patient with renal function impairment, protein binding may be decreased by 1 to 1.5%. Distributed in tissue, particularly gastric parietal cells. Apparent oral volume of distribution following administration of 30 mg of lansoprazole is about 0.5 L/kg. Since lansoprazole is acid-labile, it is administered as a capsule containing enter-coated granules to prevent gastric decomposition and to increase bioavailability. Once lansoprazole has left the stomach, absorption is rapid and relatively complete, with absolute bioavailability over 80%. Bioavailability may be decreased if lansoprazole is administered within 30 minutes of food intake as compared to that of a fasting state. Absorption may be delayed in patients with hepatic cirrhosis. Elimination: Renal: Approximately 14 to 25% of a dose of lansoprazole is excreted in the urine, as conjugated and unconjugated hydroxylated metabolites. Less than 1% of unchanged lansoprazole is detectable in the urine. Biliary/fecal: Approximately two-thirds of a dose of lansoprazole is detected as metabolites in the feces. In dialysis: Lansoprazole and its metabolites are not significantly dialyzed; no appreciable fraction is removed by hemodialysis. Note: Elimination is prolonged in healthy elderly subjects, in adult and elderly patient with mild renal impairment, and in patients with severe liver disease. For more Absorption, Distribution and Excretion (Complete) data for LANSOPRAZOLE (6 total), please visit the HSDB record page. Metabolism / Metabolites Lansoprazole is predominantly metabolized in the liver by CYP3A4 and CYP2C19. The resulting major metabolites are 5-hydroxy lansoprazole and the sulfone derivative of lansoprazole. Lansoprazole is extensively metabolized in the liver to two main excretory metabolites that are inactive. In the acidic environment of the gastric parietal cell, lansoprazole is converted to two active compounds that inhibit acid secretion by (H+,K+)-ATPase within the parietal cell canaliculus, but that are not present in the systemic circulation. Biological Half-Life One source reports the half life of lansoprazole to be 0.9 - 1.6 hours, while another source cites 0.9 - 2.1 hours. The general consensus is that lansoprazole has a short half life and is approximately 2 hours or less. These numbers may be misleading since it suggests that lansoprazole has a short duration of action when in practice, lansoprazole can effectively inhibit acid secretion for ~24 hours due to it's mechanism of action. Elimination: Normal renal function: Approximately 1.5 hours. Renal function impairment: Shortened elimination half-life. Elderly patients: 1.9 to 2.9 hours. Hepatic function impairment: 3.2 to 7.2 hours. Human oral bioavailability of Lansoprazole is approximately 85%, with a peak plasma concentration (Cmax) of 1.2 μM achieved 1.5 hours after 30 mg oral administration [1] - Lansoprazole is metabolized by hepatic cytochrome P450 enzymes (CYP1A2, CYP3A4), with a terminal half-life (t1/2) of 1.5-2 hours in humans [1] - Human plasma protein binding rate of Lansoprazole is 97% at therapeutic concentrations [1] - Lansoprazole inhibits CYP1A2 activity, reducing the metabolism of co-administered theophylline [1] |
| Toxicity/Toxicokinetics |
Hepatotoxicity Despite its wide use, lansoprazole has only rarely been associated with hepatic injury. In large scale, long term trials of lansoprazole, serum ALT elevations have occurred in less than 1% of patients and at rates similar to those that occur with placebo or comparator drugs. Only a small number of cases of clinically apparent liver disease due to lansoprazole or dexlansoprazole have been published and most have been anicteric and mild. In most instances, the time to onset was within 2 to 4 weeks and the pattern of enzyme elevations was hepatocellular or mixed. Hypersensitivity reactions with fever, rash and eosinophilia have been described due to dexlansoprazole and lansoprazole, and these reactions may be accompanied by minor serum enzyme elevations and thus qualify for DRESS syndrome (drug-rash with eosinophilia and systemic symptoms). Autoantibody formation is rare. Recovery is usually rapid (within a month) and complete upon stopping lansoprazole. Recurrence on reexposures has been reported. Likelihood score: C (probable rare cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of lansoprazole during breastfeeding. However, lansoprazole has been used safely in newborn infants, so it is unlikely that the amount in breastmilk would be harmful. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk The Spanish pharmacovigilance system found 3 cases of gynecomastia associated with lansoprazole reported during the time period of 1982 to 2006. A retrospective claims database study in the United States found that users of proton pump inhibitors had an increased risk of gynecomastia. A review article reported that a search of database from the European Pharmacovigilance Centre found 45 cases of gynecomastia, 11 cases of galactorrhea, 3 cases of breast pain and 5 cases of breast enlargement associated with lansoprazole. A search of the WHO global pharmacovigilance database found 123 cases of gynecomastia, 30 cases of galactorrhea, 36 cases of breast pain and 18 cases of breast enlargement associated with lansoprazole. In a retrospective study, out of total of 127 cases of gynecomastia in of 175 male patients, 11 patients were treated had been treated with lansoprazole. One case of elevated serum prolactin and galactorrhea was reported in a 21-year-old man. When omeprazole was substituted for lansoprazole, the serum prolactin decreased to the normal range and galactorrhea ceased. Although this case occurred in Spain, it was not included in the report above. A 13-year-old girl with a recent history of bilateral galactorrhea and hyperprolactinemia from omeprazole and domperidone on separate occasions was given lansoprazole to prevent gastrointestinal irritation following intravenous diclofenac for a severe headache. After 3 days of lansoprazole therapy, she again developed galactorrhea and an elevated serum prolactin that returned to normal a week after discontinuing lansoprazole. A 17-year-old woman using a progestin-containing IUD for 1 year began lansoprazole 15 mg daily and presented after 1 week with bilateral galactorrhea and hyperprolactinemia of 92 mcg/L. Seventy-two hours after discontinuation of lansoprazole, galactorrhea ceased. Four months later, serum prolactin was normal at 24.1 mcg/L with no recurrence of galactorrhea. The authors judged the adverse reaction likely to be caused by lansoprazole. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Protein Binding 97% of lansoprazole is plasma protein bound. Interactions Possible interactions of lansoprazole with medications known to be metabolized by the hepatic cytochrome p450 enzyme system should be considered. ... Lansoprazole, by increasing gastric pH, as the potential to affect the bioavailability of any medication whose absorption is pH-dependent. Also, lansoprazole may prevent the degradation of acid-labile drugs. Lansoprazole causes prolonged inhibition of gastric acid secretion, and thereby my interfere with the absorption of these medications /ampicillin ester, digoxin, iron salts, ketoconazole/and other for which bioavailability is determined by gastric pH. Lansoprazole appears to produce a dose-dependent decrease in the absorption of cyanocobalamin; this my be due to lansoprazole-induced hypochlorhydria or achlorhydria. For more Interactions (Complete) data for LANSOPRAZOLE (9 total), please visit the HSDB record page. In healthy volunteers receiving Lansoprazole 30 mg/day for 7 days, no significant adverse reactions were observed; hematological parameters (WBC, RBC, platelets) and liver/kidney function indices (ALT, AST, creatinine) remained within normal ranges [1] - In mice treated with Lansoprazole 10 mg/kg/day for 4 weeks, no body weight loss (<3%) or histopathological abnormalities were detected in liver, kidney, heart, or brain [3] |
| References |
[1]. Effects of lansoprazole on pharmacokinetics and metabolism of theophylline. Eur J Clin Pharmacol, 1995. 48(5): p. 391-5. [2]. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1322-1330. [3]. Defensive effect of lansoprazole in dementia of AD type in mice exposed to streptozotocin and cholesterol enriched diet. PLoS One. 2013 Jul 31;8(7):e70487. [4]. A comparative study on the modes of action of TAK-438, a novel potassium-competitive acid blocker, and lansoprazole in primary cultured rabbit gastric glands. Biochem Pharmacol. 2011 May 1;81(9):1145-51. [5]. Proton pump inhibitors omeprazole and lansoprazole induce relaxation of isolated human arteries. Eur J Pharmacol. 2006 Feb 15;531(1-3):226-31. |
| Additional Infomation |
Therapeutic Uses Antiulcerative Lansoprazole is indicated for the short-term treatment of heartburn and other symptoms associated with gastroesophageal reflux disease (GERD). Lansoprazole is indicated for the short-term (up to 8 weeks) treatment for symptom relief and healing of all grades of erosive esophagitis (associated with GERD). Lansoprazole may be indicated for an additional 8 weeks of treatment of patients in whom healing has not occurred. If erosive esophagitis recurs, an additional course of lansoprazole treatment may be considered. Lansoprazole also is indicated to maintain healing of erosive esophagitis. /Included in US product labeling/ Lansoprazole is indicated for short-term (up to 8 weeks) treatment in patients with active benign gastric ulcer. /Included in US product labeling/ Lansoprazole is indicated for short-term (up to 4 weeks) treatment for symptom relief and healing in patients with active duodenal ulcer. Lansoprazole also is indicated to maintain healing of duodenal ulcers. /Included in US product labeling/ For more Therapeutic Uses (Complete) data for LANSOPRAZOLE (6 total), please visit the HSDB record page. Drug Warnings Worldwide, over 10,000 patients have been treated with lansoprazole in Phase 2-3 trials involving various dosages and durations of treatment. The adverse reaction profiles for prevacid delayed-release capsules and prevacid for delayed-release oral suspension are similar. In general, lansoprazole treatment has been well-tolerated in both short-term and long-term trials. ... The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea. An 85-year-old white man presented with an upper gastrointestinal hemorrhage from a gastric ulcer. His platelet count was normal on admission. He was started on oral lansoprazole 60 mg twice daily and, on hospital day 2, his platelet count decreased to 102 x 10(3)/mm(3); on hospital day 3, the platelet count was 36 x 10(3)/mm(3). Lansoprazole was discontinued, and the platelet count returned to normal. He has not had any further episodes of thrombocytopenia to date. After exclusion of other causes, the onset of thrombocytopenia after administration of lansoprazole, the resolution of the adverse reaction after discontinuation of the drug, and the fact that no other medicines were introduced during this time frame lead us to believe that this was most likely an idiosyncratic thrombocytopenic response to lansoprazole. To date, this is the first reported case of what appears to be isolated thrombocytopenia associated with lansoprazole. Studies in elderly patients indicate that the clearance of lansoprazole is decreased in the elderly, resulting in a 50 to 100% increase in the elimination half-life. Because the mean half-life in the elderly remains between 1.9 and 2.9 hours, repeated once-daily dosing does not result in accumulation of lansoprazole. However, subsequent doses higher than 30 mg a day should not be administered unless additional gastric acid suppression is necessary. Diarrhea is one of the most frequently reported adverse events during proton pump inhibitor use in any setting. Because of the limited available information, this study was set up with the aim of assessing the incidence and characteristics of diarrhea and to investigate possible associated co-factors in proton pump inhibitor users in daily practice. Data were used from a prospective, observational study in which 10,008 lansprazole users were followed over time (1994-1998). The study was designed according to the SAMM guidelines. A nested case-control design was used to compare proton pump inhibitor users reporting diarrhea with those reporting no diarrhea. The frequency of diarrhea was 3.7% and the incidence density 10.7 per 1000 patients months of proton pump inhibitor use. The diarrhea was most commonly loose and occurred on average 4.4 times per day. The analysis of co-factors revealed that patients with concomitant use of oral antibiotics and patients reporting neurological and/or dermatological adverse events, were at risk of developing diarrhea during proton pomp inhibitor use. For more Drug Warnings (Complete) data for LANSOPRAZOLE (8 total), please visit the HSDB record page. Pharmacodynamics Lansoprazole decreases gastric acid secretion by targeting H+,K+-ATPase, which is the enzyme that catalyzes the final step in the acid secretion pathway in parietal cells. Conveniently, lansoprazole administered any time of day is able to inhibit both daytime and nocturnal acid secretion. The result is that lansoprazole is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn Lansoprazole also reduces pepsin secretion, making it a useful treatment option for hypersecretory conditions such as Zollinger-Ellison syndrome. Lansoprazole is a second-generation proton pump inhibitor (PPI) clinically indicated for the treatment of acid-related diseases, including gastric ulcer, duodenal ulcer, and gastroesophageal reflux disease [4] Its core mechanism of action is irreversible binding to gastric parietal cell H+/K+-ATPase, blocking H+ secretion into the gastric lumen and suppressing acid production [4] Beyond acid inhibition, it exhibits potential additional activities: inhibiting cancer cell exosome release, inducing relaxation of isolated human arteries, and exerting neuroprotective effects in AD-type dementia mouse models [2][3][5] It undergoes hepatic metabolism via CYP450 enzymes, and co-administration with CYP1A2 substrates requires dosage adjustment to avoid excessive drug accumulation [1] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.77 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 (6.77 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 | 2.7074 mL | 13.5369 mL | 27.0739 mL | |
| 5 mM | 0.5415 mL | 2.7074 mL | 5.4148 mL | |
| 10 mM | 0.2707 mL | 1.3537 mL | 2.7074 mL |