Lansoprazole (AG 1749) primarily targets gastric parietal cell H+/K+-ATPase (IC50 = 0.8 μM for inhibiting H+/K+-ATPase activity) [4]

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].

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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]

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].

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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]

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]

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/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.

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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]

Absorption, Distribution and Excretion
Lansoprazole has been reported to have an oral bioavailability of 80-90%, reaching peak plasma concentration (Cmax) approximately 1.7 hours after oral administration. Food reduces the absorption of lansoprazole (both Cmax and AUC decrease by 50-70%); therefore, patients should be instructed to take lansoprazole before meals. 14-23% of lansoprazole has been reported to be excreted in the urine; this percentage range includes both bound and unbound hydroxylated metabolites. The apparent volume of distribution of lansoprazole is 0.4 L/kg. Lansoprazole has been reported to have a clearance rate of 400-650 mL/min. Protein binding is very high (approximately 97%); it remains constant within the concentration range of 0.05 to 5 μg/mL. Protein binding may be reduced by 1% to 1.5% in patients with impaired renal function. Lansoprazole is distributed in tissues, particularly in gastric parietal cells. The apparent volume of distribution after oral administration of 30 mg lansoprazole is approximately 0.5 L/kg. Because lansoprazole is unstable in acid, it is usually administered in enteric-coated granule capsules to prevent gastric breakdown and improve bioavailability. Lansoprazole is rapidly and relatively completely absorbed after leaving the stomach, with an absolute bioavailability exceeding 80%. Taking lansoprazole within 30 minutes after a meal may reduce its bioavailability compared to a fasting state. Absorption may be delayed in patients with cirrhosis. Excretion: Renal: Approximately 14% to 25% of the lansoprazole dose is excreted in the urine as conjugated and unconjugated hydroxylated metabolites. Less than 1% of the unchanged lansoprazole is detectable in the urine. Bile/Feces: Approximately two-thirds of the lansoprazole dose is detected in the feces as metabolites. Dialysis: Lansoprazole and its metabolites are poorly removed by dialysis; they are almost impossible to remove by hemodialysis. Note: Drug clearance time is prolonged in healthy elderly individuals, adults and elderly patients with mild renal impairment, and patients with severe hepatic disease. For more complete data on the absorption, distribution, and excretion of lansoprazole (6 types), please visit the HSDB record page.

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Metabolism/Metabolites
Lansoprazole is primarily metabolized in the liver via CYP3A4 and CYP2C19. The major metabolites are 5-hydroxylansoprazole and lansoprazole sulfone derivatives.
Lansoprazole is extensively metabolized in the liver to two major excretory metabolites, both of which are inactive. In the acidic environment of gastric parietal cells, lansoprazole is converted into two active compounds that inhibit gastric acid secretion via (H+,K+)-ATPase in the parietal tubules but do not enter systemic circulation.

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Biological Half-Life
Data indicate that the half-life of lansoprazole is 0.9–1.6 hours, while other data indicate 0.9–2.1 hours. It is generally believed that lansoprazole has a short half-life, approximately 2 hours or less. These data may be misleading, as they suggest a short duration of action; in reality, due to its mechanism of action, lansoprazole can effectively inhibit gastric acid secretion for approximately 24 hours. Elimination: Normal renal function: approximately 1.5 hours. Impaired renal function: shortened elimination half-life. Elderly patients: 1.9 to 2.9 hours. Hepatic impairment: 3.2 to 7.2 hours.

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The oral bioavailability of lansoprazole in humans is approximately 85%, and the peak plasma concentration (Cmax) of 1.2 μM is reached 1.5 hours after oral administration of 30 mg [1]. Lansoprazole is metabolized by hepatic cytochrome P450 enzymes (CYP1A2, CYP3A4), and its terminal half-life (t1/2) in the human body is 1.5-2 hours [1]. Lansoprazole has a plasma protein binding rate of 97% at therapeutic concentrations [1]. Lansoprazole inhibits CYP1A2 activity, thereby reducing the metabolism of theophylline when used in combination [1].

Hepatotoxicity
Despite the widespread use of lansoprazole, cases of liver injury caused by it are extremely rare. In large-scale long-term trials of lansoprazole, the incidence of elevated serum ALT was less than 1%, similar to that of placebo or control drugs. Only a few cases of clinically significant liver disease caused by lansoprazole or dextrolansoprazole have been reported, and most cases were mild and without jaundice. In most cases, onset is 2 to 4 weeks, with hepatocellular or mixed patterns of enzyme elevation. Dextrolansoprazole and lansoprazole have been reported to cause hypersensitivity reactions with fever, rash, and eosinophilia, which may be accompanied by mild serum enzyme elevations, thus meeting the diagnostic criteria for DRESS syndrome (drug-induced rash with eosinophilia and systemic symptoms). Autoantibody formation is rare. Recovery after discontinuation of lansoprazole is usually rapid (within one month) and complete. Relapse upon re-exposure has been reported. Probability score: C (likely a rare cause of clinically significant liver injury).

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Effects during pregnancy and lactation
◉ Overview of use during lactation
There is currently no information regarding the use of lansoprazole during lactation. However, lansoprazole has been safely used in newborns, so the amount in breast milk is unlikely to be harmful.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
The Spanish pharmacovigilance system reported three cases of gynecomastia associated with lansoprazole between 1982 and 2006. A retrospective US claims database study found an increased risk of gynecomastia in users of proton pump inhibitors.
A review article reported that a search of the European Pharmacovigilance Center database 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 World Health Organization's Global Pharmacovigilance Database revealed 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, 127 cases of gynecomastia occurred in 175 male patients, 11 of whom had previously received lansoprazole treatment. Another case involved a 21-year-old male patient who reported elevated serum prolactin and galactorrhea. When lansoprazole was replaced with omeprazole, serum prolactin levels returned to normal, and the galactorrhea resolved. Although this case occurred in Spain, it was not included in the aforementioned reports. A 13-year-old girl, who had recently experienced bilateral galactorrhea and hyperprolactinemia after taking omeprazole and domperidone respectively, received intravenous diclofenac sodium for severe headache to prevent gastrointestinal irritation and was treated with lansoprazole. Three days after lansoprazole treatment, she experienced galactorrhea and elevated serum prolactin again; she recovered after one week of discontinuing lansoprazole. A 17-year-old female, who had been using a progestin-containing intrauterine device for one year, started taking 15 mg of lansoprazole daily. One week later, she developed bilateral galactorrhea and elevated prolactin levels (92 μg/L). The galactorrhea stopped 72 hours after lansoprazole was discontinued. Four months later, serum prolactin levels returned to normal at 24.1 mcg/L, and the galactorrhea did not recur. The authors believe this adverse reaction was most likely caused by lansoprazole. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed. Protein Binding: 97% of lansoprazole is bound to plasma proteins. Drug Interactions: Potential interactions between lansoprazole and drugs known to be metabolized by the hepatic cytochrome P450 enzyme system should be considered. Lansoprazole may affect the bioavailability of any pH-dependent drug by increasing gastric pH. Furthermore, lansoprazole may inhibit the degradation of acid-labile drugs. Lansoprazole can cause long-term inhibition of gastric acid secretion, thereby interfering with the absorption of certain drugs (such as ampicillin, digoxin, iron salts, ketoconazole, etc.) and other drugs whose bioavailability is affected by gastric pH. Lansoprazole appears to reduce the absorption of cyanocobalamin in a dose-dependent manner; this may be due to gastric acid deficiency or reduction caused by lansoprazole. For more complete data on interactions of lansoprazole (9 in total), please visit the HSDB record page. In healthy volunteers who received lansoprazole 30 mg/day for 7 days, no significant adverse reactions were observed; hematological parameters (white blood cells, red blood cells, platelets) and liver and kidney function indicators (ALT, AST, creatinine) were within the normal range [1]. In mice treated with lansoprazole 10 mg/kg/day for 4 weeks, no weight loss (<3%) or pathological abnormalities in liver, kidney, heart or brain tissue were detected [3].

[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.

Therapeutic Uses
Lansoprazole is indicated for short-term treatment of heartburn and other symptoms associated with gastroesophageal reflux disease (GERD). Lansoprazole is indicated for short-term (maximum 8 weeks) treatment to relieve and heal all grades of erosive esophagitis (associated with GERD). For patients whose esophagitis has not healed, lansoprazole may be used for an additional 8 weeks of treatment. If erosive esophagitis recurs, lansoprazole treatment may be considered again. Lansoprazole is also indicated for maintaining the healing of erosive esophagitis. /US product label includes/ Lansoprazole is indicated for short-term (maximum 8 weeks) treatment of patients with active benign gastric ulcers. /US product label includes/ Lansoprazole is indicated for short-term (maximum 4 weeks) treatment of active duodenal ulcers to relieve symptoms and promote ulcer healing. Lansoprazole is also indicated for maintaining the healing of duodenal ulcers. /US Product Label Contains/
For more complete data on the therapeutic uses of lansoprazole (6 items of total), please visit the HSDB Records page.

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Drug Warnings
Globally, more than 10,000 patients have received lansoprazole in Phase II and III clinical trials involving different doses and durations. The adverse reaction profiles of prevasci extended-release capsules and prevasci extended-release oral suspension are similar. Overall, lansoprazole treatment has been well tolerated in both short-term and long-term trials. The most frequently reported possible or likely treatment-related adverse event during maintenance therapy is diarrhea.
An 85-year-old white male was admitted to the hospital with upper gastrointestinal bleeding due to a gastric ulcer. His platelet count was normal upon admission. He was given lansoprazole orally at 60 mg twice daily after admission. On day 2 of admission, his platelet count decreased to 102 × 10³/mm³; on day 3 of admission, his platelet count decreased to 36 × 10³/mm³. After discontinuation of lansoprazole, the platelet count returned to normal. He has not experienced thrombocytopenia since. Having ruled out other causes, the patient developed thrombocytopenia after taking lansoprazole, which resolved upon discontinuation, and no other medications were taken during this period. Therefore, we believe this is likely lansoprazole-specific thrombocytopenia. This is the first reported case of isolated thrombocytopenia associated with lansoprazole to date. Studies in elderly patients have shown that lansoprazole clearance is reduced in older adults, resulting in a 50% to 100% prolonged elimination half-life. Since the mean half-life in older adults remains between 1.9 and 2.9 hours, repeated once-daily dosing does not lead to lansoprazole accumulation. However, unless additional gastric acid suppression is required, a dose exceeding 30 mg daily should not be taken. Diarrhea is one of the most common adverse reactions during proton pump inhibitor (PPI) use. Due to limited relevant information, this study aimed to assess the incidence and characteristics of diarrhea in routine practice among PPI users and to explore possible contributing factors. This study used data from a prospective observational study that followed 10,008 lansoprazole users (1994–1998). The study design followed SAMM guidelines. A nested case-control design was used to compare proton pump inhibitor (PPI) users who reported diarrhea with those who did not. The incidence of diarrhea was 3.7%, with a monthly incidence of 10.7 per 1000 patients using PPIs. Loose stools were the most common type of diarrhea, occurring an average of 4.4 times per day. Analysis of relevant factors indicated that patients taking oral antibiotics concurrently and those who reported neurological and/or skin adverse reactions had a higher risk of developing diarrhea during PPI use.
For more complete data on drug warnings for lansoprazole (8 of 8), please visit the HSDB record page.

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Pharmacodynamics
Lansoprazole reduces gastric acid secretion by targeting H+,K+-ATPase, the final step in the parietal cell acid secretion pathway. Lansoprazole can be taken at any time of day to inhibit gastric acid secretion during the day and night. Results show that lansoprazole is effective in treating duodenal ulcers, reducing ulcer-related pain, and relieving heartburn. Lansoprazole also reduces pepsin secretion, making it an effective option for treating hyperacidity syndromes such as Zollinger-Ellison syndrome. Lansoprazole is a second-generation proton pump inhibitor (PPI) used clinically to treat acid-related diseases, including gastric ulcers, duodenal ulcers, and gastroesophageal reflux disease [4]. Its core mechanism of action is to irreversibly bind to H+/K+-ATPase in gastric parietal cells, blocking H+ secretion into the gastric lumen, thereby inhibiting gastric acid secretion [4]. In addition to inhibiting gastric acid secretion, lansoprazole also has other potential activities: inhibiting the release of exosomes from cancer cells, inducing diastole of isolated human arteries, and exerting neuroprotective effects in a mouse model of Alzheimer's disease. [2][3][5]
It is metabolized in the liver by the CYP450 enzyme, and dosage adjustment is required when used in combination with CYP1A2 substrates to avoid excessive drug accumulation[1]

C16H14F3N3O2S

369.36

369.075

103577-45-3

(R)-Lansoprazole;138530-94-6;Lansoprazole-d4;934294-22-1;(S)-Lansoprazole;138530-95-7

3883

White to off-white solid powder

1.5±0.1 g/cm3

555.8±60.0 °C at 760 mmHg

178-182°C dec.

289.9±32.9 °C

0.0±1.5 mmHg at 25°C

1.635

2.76

1

8

5

25

480

0

MJIHNNLFOKEZEW-UHFFFAOYSA-N

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)

2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]-1H-benzimidazole

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)

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.

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)