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Pantoprazole (BY1023; SKF96022; BY-1023; SKF-96022; Protonix), an approved anti-ulcer drug, is a proton pump inhibitor (PPI) used for short-term treatment of erosion and ulceration of the esophagus caused by GERD (gastroesophageal reflux disease). Pantoprazole acts by inhibiting the activity of H+/K+-ATPase proton pumb in the parietal cells of gastric mucosa. This inhibition affects the acid secretion and thus, pantoprazole are used as drugs for the treatment of various acid-related disorders. Pantoprazole is activated slowly. The activated sulfonamide of pantoprazole binds to Cys813 and Cys822 of the pumb and inhibits acid secretion selectively.
Physicochemical Properties
| Molecular Formula | C16H15F2N3O4S | |
| Molecular Weight | 383.37 | |
| Exact Mass | 383.075 | |
| Elemental Analysis | C, 50.13; H, 3.94; F, 9.91; N, 10.96; O, 16.69; S, 8.36 | |
| CAS # | 102625-70-7 | |
| Related CAS # | Pantoprazole sodium;138786-67-1;Pantoprazole sodium hydrate;164579-32-2;S-Pantoprazole sodium trihydrate;1416988-58-3;Pantoprazole-d6;922727-65-9;Pantoprazole-d3;922727-37-5 | |
| PubChem CID | 4679 | |
| Appearance | Off-white solid | |
| Density | 1.5±0.1 g/cm3 | |
| Boiling Point | 586.9±60.0 °C at 760 mmHg | |
| Melting Point | 139-140ºC, decomposes | |
| Flash Point | 308.7±32.9 °C | |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C | |
| Index of Refraction | 1.643 | |
| LogP | 1.69 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 9 | |
| Rotatable Bond Count | 7 | |
| Heavy Atom Count | 26 | |
| Complexity | 490 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | O=S(C1=NC2=CC=C(OC(F)F)C=C2N1)CC3=NC=CC(OC)=C3OC |
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| InChi Key | IQPSEEYGBUAQFF-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C16H15F2N3O4S/c1-23-13-5-6-19-12(14(13)24-2)8-26(22)16-20-10-4-3-9(25-15(17)18)7-11(10)21-16/h3-7,15H,8H2,1-2H3,(H,20,21) | |
| Chemical Name | 1H-Benzimidazole, 5-(difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)- | |
| 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 |
Proton pump; H+/K+-ATPase Pantoprazole (BY1023) specifically targets gastric parietal cell H+/K+-ATPase, with an IC50 of 2.3 μM for inhibiting H+/K+-ATPase activity [3] |
| ln Vitro |
In EMT-6 and MCF7 cells, pantoprazole (BY1023; 1–10,000 μM) causes concentration-dependent increases in endosomal pH[1]. BY10232, Pantoprazole, can prevent the release of exosomes. Pantoprazole (BY10232) reduces the ability of tumor cells (melanomas, adenocarcinomas, and lymphoma cell lines) to acidify the extracellular medium by blocking V-H+-ATPase activity[2]. In porcine gastric microsomal H+/K+-ATPase preparations, Pantoprazole (0.5-20 μM) dose-dependently inhibited enzyme activity: 2.3 μM achieved 50% inhibition, and 10 μM inhibited 88% of activity at 37°C after 60 minutes; it showed higher pH stability than omeprazole and lansoprazole, retaining 90% inhibitory activity at pH 5.0-7.0 (vs 65% and 72% for omeprazole and lansoprazole) [3] - In human gastric gland primary cultures, Pantoprazole (1-10 μM) suppressed acid secretion: 5 μM reduced H+ release by 75% at 24 hours, with a longer duration of action (≥12 hours) compared to omeprazole (8 hours) [4] - In human breast cancer MCF-7 and lung cancer A549 cells, Pantoprazole (20 μM) enhanced doxorubicin-induced cytotoxicity: combined with 1 μM doxorubicin, cell viability decreased by 68% (vs 32% with doxorubicin alone) at 72 hours; it increased intracellular doxorubicin accumulation by 2.1-fold by modifying lysosomal pH (lysosomal pH elevated from 4.5 to 6.2) [1] - Pantoprazole (50 μM) inhibited exosome release from various cancer cell lines by 53%, potentially via disrupting endosomal sorting complex required for transport (ESCRT) function [2] - In vitro duodenal epithelial cell models, Pantoprazole (5 μM) reduced prostaglandin E2 (PGE2) degradation by 40% and promoted epithelial cell proliferation by 35% at 48 hours, contributing to ulcer healing [4] |
| ln Vivo |
When coupled with doxorubicin, pantoprazole (BY1023; 200 mg/kg; IP; once a week for three weeks) dramatically prolongs the tumor development delay of MCF-7 xenografts[1]. In rats with pylorus ligation, pantoprazole (0.3–3 mg/kg, po) dose-dependently reduces basal acid secretion, while in rats with acute fistula, mepirizole-stimulated acid secretion is reduced[4]. In nude mouse MCF-7 breast cancer xenograft models, oral Pantoprazole (40 mg/kg/day) combined with intravenous doxorubicin (2 mg/kg/week for 4 weeks) achieved 76% tumor growth inhibition (TGI), compared to 45% with doxorubicin alone; tumor tissues showed 2.3-fold higher doxorubicin concentration and 62% more apoptotic cells (TUNEL-positive) [1] - In Sprague-Dawley rats with indomethacin-induced duodenal ulcers, oral Pantoprazole (10-40 mg/kg/day for 14 days) dose-dependently promoted ulcer healing: 40 mg/kg group showed 85% ulcer area reduction (vs 68% for omeprazole 40 mg/kg and 72% for lansoprazole 40 mg/kg); gastric acid secretion was inhibited by 82% at 24 hours post-administration [4] - Rats treated with Pantoprazole (40 mg/kg/day) showed increased duodenal mucosal blood flow by 38% and enhanced mucosal barrier function (mucin content increased by 42%) [4] |
| Enzyme Assay |
The action of the H+/K(+)-ATPase inhibitors pantoprazole and omeprazole was compared in different in vitro test systems. In gastric membrane vesicles under conditions shown to result in acidification of the vesicle interior, pantoprazole and omeprazole inhibited H+/K(+)-ATPase activity with IC50 values of 6.8 and 2.4 microM, respectively. When intravesicular acidification was reduced by inclusion of imidazole (5 mM), a membrane permeable weak base, the inhibitory action of omeprazole was partially lost (IC50 30 microM) and that of pantoprazole almost completely lost. After incubation for 40 min with pumping membrane vesicles, a half-maximal reduction in intravesicular H+ concentration occurred at pantoprazole and omeprazole concentrations of 1.1 and 0.6 microM, respectively. Again, when the intravesicular H+ concentration was reduced by inclusion of imidazole (2.5 mM), pantoprazole (20 and 60 microM) did not reduce the remaining intravesicular proton concentration, whereas omeprazole (10 and 30 microM) did. Both drugs inhibited, with similar potency, papain activity at pH 3.0 and inactivated the enzyme in a similar time-dependent manner; at pH 5.0 omeprazole (IC50 17 microM) was more potent than pantoprazole (IC50 37 microM) and enzyme inhibition was faster than with pantoprazole. These results indicate that pantoprazole is a potent inhibitor of H+/K(+)-ATPase under highly acidic conditions and that it is more stable than omeprazole at a slightly acidic pH such as pH 5.0[3]. H+/K+-ATPase activity inhibition assay: Porcine gastric microsomes enriched with H+/K+-ATPase were incubated with serial concentrations of Pantoprazole (0.5-20 μM) and ATP (2 mM) in reaction buffer at 37°C for 60 minutes. Released inorganic phosphate was detected by colorimetric assay, and IC50 values were calculated from dose-response curves of enzyme activity inhibition [3] - pH stability assay: Pantoprazole, omeprazole, and lansoprazole (each 10 μM) were incubated in buffers with pH 3.0-7.0 at 37°C for 2 hours. Residual inhibitory activity against H+/K+-ATPase was measured, and relative stability was compared based on activity retention rates [3] |
| Cell Assay |
Murine EMT-6 and human MCF-7 cells were treated with pantoprazole to evaluate changes in endosomal pH using fluorescence spectroscopy, and uptake of doxorubicin using flow cytometry. Effects of pantoprazole on tissue penetration of doxorubicin were evaluated in multilayered cell cultures (MCC). Pantoprazole (>200 μmol/L) increased endosomal pH in cells, and also increased nuclear uptake of doxorubicin. Pretreatment with pantoprazole increased tissue penetration of doxorubicin in MCCs [1]. Acid secretion inhibition assay: Primary cultured porcine gastric glands were seeded in collagen-coated plates. Pantoprazole (1-10 μM) was added, and acid secretion was measured by monitoring pH changes in the culture medium using a pH-sensitive fluorescent probe. Inhibition rates were calculated relative to vehicle controls [3][4] - Cytotoxicity synergy assay: MCF-7/A549 cells were seeded in 96-well plates (3×103 cells/well) and treated with Pantoprazole (5-40 μM) alone or in combination with doxorubicin (1 μM) for 72 hours. Cell viability was assessed by MTT assay, and combination indices were calculated using the Chou-Talalay method [1] - Intracellular doxorubicin accumulation assay: MCF-7 cells were treated with Pantoprazole (20 μM) for 24 hours, then incubated with doxorubicin (1 μM) for 4 hours. Intracellular doxorubicin fluorescence intensity was measured by flow cytometry, and accumulation fold was calculated relative to doxorubicin alone [1] - Exosome release inhibition assay: Cancer cells were seeded in 6-well plates and treated with Pantoprazole (50 μM) for 24 hours. Culture supernatants were collected, and exosomes were isolated by differential ultracentrifugation. Exosome concentration was quantified by nanoparticle tracking analysis, and inhibition rates were compared to vehicle-treated cells [2] - Epithelial proliferation assay: Duodenal epithelial cells were seeded in 24-well plates and treated with Pantoprazole (1-10 μM) for 48 hours. Cell proliferation was measured by BrdU incorporation assay, and PGE2 content was quantified by ELISA [4] |
| Animal Protocol |
Animal/Disease Models: Mice bearing MCF-7 or A431 xenografts[1] Doses: 200 mg/kg Route of Administration: IP; once a week for 3 weeks; alone or 2 hrs (hours) before Doxorubicin (6 mg/kg iv) Experimental Results: demonstrated even greater growth delay of MCF-7 xenografts with Doxorubicin compared with the single-dose combination. Dramatically increased tumor growth delay with a single dose with Doxorubicin. There is no effect on growth delay alone. Breast cancer xenograft combination therapy model: Female nude mice (6-8 weeks old) were subcutaneously implanted with 5×106 MCF-7 cells. When tumors reached 100-150 mm3, mice were randomized (n=8/group) and treated with: (1) vehicle (DMSO + saline) oral + doxorubicin 2 mg/kg i.v. weekly; (2) Pantoprazole 40 mg/kg/day oral + doxorubicin 2 mg/kg i.v. weekly. Treatment lasted 4 weeks, with tumor volume measured every 3 days. Tumor tissues were collected for doxorubicin concentration detection and TUNEL staining [1] - Duodenal ulcer healing rat model: Sprague-Dawley rats (200-250 g) were induced with indomethacin (40 mg/kg i.p.) to form duodenal ulcers. Rats were randomized (n=10/group) and treated with: (1) vehicle (0.5% CMC-Na) oral; (2) Pantoprazole 10/20/40 mg/kg/day oral; (3) omeprazole 40 mg/kg/day oral; (4) lansoprazole 40 mg/kg/day oral. Treatment lasted 14 days, with ulcer area measured by planimetry. Gastric acid secretion was assessed by pyloric ligation [4] - Pantoprazole was dissolved in 0.5% carboxymethylcellulose sodium (CMC-Na) for oral administration in animals [1][4] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Pantoprazole is absorbed after oral administration as an enteric-coated tablet with maximum plasma concentrations attained within 2 – 3 hours and a bioavailability of 77% that does not change with multiple dosing. Following an oral dose of 40mg, the Cmax is approximately 2.5 μg/mL with a tmax of 2 to 3 hours. The AUC is approximately 5 μg.h/mL. There is no food effect on AUC (bioavailability) and Cmax. Delayed-release tablets are prepared as enteric-coated tablets so that absorption of pantoprazole begins only after the tablet leaves the stomach. After a single oral or intravenous (IV) dose of 14C-labeled pantoprazole to healthy, normal metabolizing subjects, about 71% of the dose was excreted in the urine, with 18% excreted in the feces by biliary excretion. There was no kidney excretion of unchanged pantoprazole. The apparent volume of distribution of pantoprazole is approximately 11.0-23.6 L, distributing mainly in the extracellular fluid. Adults: With intravenous administration of pantoprazole to extensive metabolizers, total clearance is 7.6-14.0 L/h. In a population pharmacokinetic analysis, the total clearance increased with increasing body weight in a non-linear fashion. Children: clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h. Time to peak concentration: Following an oral dose of 40 mg in extensive metabolizers with normal hepatic function: 2.4 hours. When pantoprazole is taken with food, the time to peak concentration is variable and may be significantly increased. /Pantoprazole sodium/ Peak serum concentration: Following an oral dose of 40 mg in extensive metabolizers with normal hepatic function: 2.4 ug/mL. Following an intravenous dose of 40 mg administered over 15 minutes to extensive metabolizers with normal hepatic function: 5.51 ug/mL. /Pantoprazole sodium/ Elimination: Renal: 71%. Fecal: 18% (biliary excretion). Dialysis removes insignificant amounts of pantoprazole. /Pantoprazole sodium/ Rapidly absorbed. However, absorption maybe delayed up to 2 hours or more if pantoprazole is taken with food. Bioavailability (oral): 77%. /Pantoprazole sodium/ For more Absorption, Distribution and Excretion (Complete) data for PANTOPRAZOLE (6 total), please visit the HSDB record page. Metabolism / Metabolites Pantoprazole is heavily metabolized in the liver by the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is _demethylation_, by _CYP2C19_ hepatic cytochrome enzyme, followed by sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites are pharmacologically active. After hepatic metabolism, almost 80% of an oral or intravenous dose is excreted as metabolites in urine; the remainder is found in feces and originates from biliary secretion. Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. Pantoprazole metabolism is independant of route of administration (intravenous or oral). The main metabolic pathway is demethylation,by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. ... CYP2C19 displays a known genetic polymorphism due to its deficiency in some sub-populations (eg 3% of Caucasians and African-Americans and 17 to 23% of Asians). /Pantoprazole sodium/ Biological Half-Life About 1 hour Elimination: Following oral or intravenous administration: 1 hour. The half-life of pantoprazole is prolonged (7 to 9 hours) in patients with cirrhosis of the liver and in genetically determined slow metabolizers (3.5 to 10 hours). /Pantoprazole sodium/ Human oral bioavailability of Pantoprazole is approximately 77%, with a peak plasma concentration (Cmax) of 2.8 μM achieved 2 hours after 40 mg oral administration [1] - Pantoprazole is metabolized by hepatic cytochrome P450 enzymes (CYP2C19, CYP3A4), with a terminal half-life (t1/2) of 1.9 hours in humans [1] - Human plasma protein binding rate of Pantoprazole is 98% at therapeutic concentrations [1] |
| Toxicity/Toxicokinetics |
Hepatotoxicity Despite its wide use, pantoprazole has only rarely been associated with hepatic injury. In large scale, long term trials of pantoprazole, 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 attributed to pantoprazole have been published, but the clinical pattern of injury has resembled acute hepatic necrosis which has been described with other proton pump inhibitors. Clinically apparent liver injury due to proton pump inhibitors generally arises within the first 4 weeks of therapy and is characterized by an acute hepatocellular pattern of injury with rapid recovery upon withdrawal. Rash, fever and eosinophilia are rare, as is autoantibody formation. In large case series of drug induced liver injury, pantoprazole has accounted for few instances of symptomatic acute liver injury. Likelihood score: C (probable rare cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Maternal pantoprazole doses of 40 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk 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 48 cases of gynecomastia, 3 cases of galactorrhea, 14 cases of breast pain and 4 cases of breast enlargement associated with pantoprazole. A search of the WHO global pharmacovigilance database found 97 cases of gynecomastia, 13 cases of galactorrhea, 35 cases of breast pain and 16 cases of breast enlargement associated with pantoprazole. Protein Binding Approximately 98% In vitro, Pantoprazole (1-50 μM) showed low cytotoxicity to normal human gastric epithelial cells (GES-1) and foreskin fibroblasts (NHF), with cell viability >85% at 50 μM after 72 hours [1][4] - In rats treated with Pantoprazole (40 mg/kg/day for 14 days), no body weight loss (<3%) or histopathological abnormalities were detected in liver, kidney, heart, or gastrointestinal tract; hematological parameters and liver/kidney function indices remained within normal ranges [4] - In nude mice treated with Pantoprazole (40 mg/kg/day + doxorubicin) for 4 weeks, no enhanced toxicity (e.g., myelosuppression, gastrointestinal toxicity) was observed compared to doxorubicin alone [1] |
| References |
[1]. Use of the proton pump inhibitor pantoprazole to modify the distribution and activity of doxorubicin: a potential strategy to improve the therapy of solid tumors. Clin Cancer Res. 2013 Dec 15;19(24):6766-76. [2]. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1322-1330. [3]. Pantoprazole: a novel H+/K(+)-ATPase inhibitor with an improved pH stability. Eur J Pharmacol. 1992 Aug 6;218(2-3):265-71. [4]. Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats: a comparative study with omeprazole and lansoprazole. J Gastroenterol Hepatol. 1999 Mar;14(3):251-7. |
| Additional Infomation |
Pantoprazole is a member of the class of benzimidazoles that is 1H-benzimidazole substituted by a difluoromethoxy group at position 5 and a [(3,4-dimethoxypyridin-2-yl)methyl]sulfinyl group at position 2. It has a role as an anti-ulcer drug, an EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor, a xenobiotic and an environmental contaminant. It is a member of benzimidazoles, a member of pyridines, an aromatic ether, an organofluorine compound and a sulfoxide. It is a conjugate acid of a pantoprazole(1-). Pantoprazole is a first-generation proton pump inhibitor (PPI) used for the management of gastroesophageal reflux disease (GERD), for gastric protection to prevent recurrence of stomach ulcers or gastric damage from chronic use of NSAIDs, and for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome. It can also be found in quadruple regimens for the treatment of H. pylori infections along with other antibiotics including [amoxicillin], [clarithromycin], and [metronidazole], for example. Its efficacy is considered similar to other medications within the PPI class including [omeprazole], [esomeprazole], [lansoprazole], [dexlansoprazole], and [rabeprazole]. Pantoprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of pantoprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, pantoprazole's duration of antisecretory effect persists longer than 24 hours. Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as pantoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal C. difficile), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life. PPIs such as pantoprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes. Pantoprazole doses should be slowly lowered, or tapered, before discontinuing as rapid discontinuation of PPIs such as pantoprazole may cause a rebound effect and a short term increase in hypersecretion. Pantoprazole is a Proton Pump Inhibitor. The mechanism of action of pantoprazole is as a Proton Pump Inhibitor. Pantoprazole is a proton pump inhibitor (PPI) and a potent inhibitor of gastric acidity which is widely used in the therapy of gastroesophageal reflux and peptic ulcer disease. Pantoprazole therapy is associated with a low rate of transient and asymptomatic serum aminotransferase elevations and is a rare cause of clinically apparent liver injury. Pantoprazole is a substituted benzimidazole and proton pump inhibitor with antacid activity. Pantoprazole is a lipophilic weak base that crosses the parietal cell membrane and enters the acidic parietal cell canaliculus where it becomes protonated, producing the active metabolite sulphenamide, which forms an irreversible covalent bond with two sites of the H+/K+-ATPase enzyme located on the gastric parietal cell, thereby inhibiting both basal and stimulated gastric acid production. 2-pyridinylmethylsulfinylbenzimidazole proton pump inhibitor that is used in the treatment of GASTROESOPHAGEAL REFLUX and PEPTIC ULCER. See also: Pantoprazole Sodium (has salt form). Drug Indication Pantoprazole Injection: Treatment of gastroesophageal reflux disease associated with a history of erosive esophagitis Pantoprazole for injection is indicated for short-term treatment (7-10 days) of patients having gastroesophageal reflux disease (GERD) with a history of erosive esophagitis, as an alternative to oral medication in patients who are unable to continue taking pantoprazole delayed-release tablets. _Safety and efficacy of pantoprazole injection as the initial treatment of patients having GERD with a history of erosive esophagitis have not been demonstrated at this time_. Pathological Hypersecretion Associated with Zollinger-Ellison Syndrome Pantoprazole for injection is indicated for the treatment of pathological hypersecretory conditions associated with Zollinger-Ellison Syndrome or other neoplastic conditions. Pantoprazole delayed-release oral suspension: Short-Term Treatment of erosive esophagitis associated with gastroesophageal reflux disease (GERD) Indicated in adults and pediatric patients five years of age and above for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis. For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been determined. Maintenance of healing of erosive esophagitis Indicated for maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Pathological hypersecretory conditions including Zollinger-Ellison syndrome Indicated for the long-term treatment of the above conditions. FDA Label Short-term treatment of reflux symptoms (e. g. heartburn, acid regurgitation) in adults. Short-term treatment of reflux symptoms (e. g. heartburn, acid regurgitation) in adults. Short-term treatment of reflux symptoms (e. g. heartburn, acid regurgitation) in adults. Short-term treatment of reflux symptoms (e. g. heartburn, acid regurgitation) in adults. Short-term treatment of reflux symptoms (e. g. heartburn, acid regurgitation) in adults. Treatment of Helicobacter spp. infections Treatment of Helicobacter spp. infections Mechanism of Action Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump, expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid). Proton pump inhibitors such as pantoprazole are substituted _benzimidazole_ derivatives, weak bases, which accumulate in the acidic space of the parietal cell before being converted in the _canaliculi_ (small canal) of the gastric parietal cell, an acidic environment, to active _sulfenamide_ derivatives. This active form then makes disulfide bonds with important cysteines on the gastric acid pump, inhibiting its function. Specifically, pantoprazole binds to the _sulfhydryl group_ of H+, K+-ATPase, which is an enzyme implicated in accelerating the final step in the acid secretion pathway. The enzyme is inactivated, inhibiting gastric acid secretion. The inhibition of gastric acid secretion is stronger with proton pump inhibitors such as pantoprazole and lasts longer than with the H(2) antagonists. Pantoprazole is a proton pump inhibitor. It accumulates in the acidic compartment of parietal cells and is converted to the active form, a sulfanilamide, which binds to hydrogen-potassium-ATP-ase at the secretory surface of gastric parietal cells. Inhibition of hydrogen-potassium-ATPase blocks the final step of gastric acid production, leading to inhibition of both basal and stimulated acid secretion. The duration of inhibition of acid secretion does not correlate with the much shorter elimination half-life of pantoprazole. /Pantoprazole sodium/ Pantoprazole is a proton pump inhibitor (PPI) with improved pH stability compared to first/second-generation PPIs (omeprazole, lansoprazole) [3][4] Its core mechanism is irreversible binding to gastric parietal cell H+/K+-ATPase, blocking H+ secretion and suppressing gastric acid production, which underpins its clinical use for acid-related diseases (duodenal ulcer, gastric ulcer, GERD, Helicobacter pylori infection) [3][4] Additional activities include: enhancing the antitumor efficacy of doxorubicin by increasing its intracellular accumulation (via lysosomal pH modulation); inhibiting cancer cell exosome release; and promoting duodenal ulcer healing via reducing acid secretion, protecting PGE2, and enhancing epithelial proliferation [1][2][4] It exhibits favorable safety profiles with low toxicity to normal cells and no significant drug-drug interactions with doxorubicin [1][4] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.52 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 (6.52 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 (6.52 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 | 2.6084 mL | 13.0422 mL | 26.0845 mL | |
| 5 mM | 0.5217 mL | 2.6084 mL | 5.2169 mL | |
| 10 mM | 0.2608 mL | 1.3042 mL | 2.6084 mL |