Proton pump
In EMT-6 and MCF7 cells, pantoprazole sodium hydrate (BY1023 sodium hydrate; 1–10,000 μM) raises endosomal pH in a concentration-dependent manner [1]. Pantoprazole sodium hydrate prevents exosome release. Pantoprazole sodium hydrate prevents tumor cells (melanoma, adenocarcinoma, and lymphoma cell lines) from acidifying the extracellular medium by inhibiting V-H+-ATPase activity [2].

在 EMT-6 和 MCF7 细胞中，泮托拉唑钠水合物（BY1023 水合钠；1–10,000 μM）以浓度依赖性方式升高内体 pH 值 [1]。泮托拉唑钠水合物可防止外泌体释放。泮托拉唑钠水合物通过抑制 V-H+-ATP 酶活性来防止肿瘤细胞（黑色素瘤、腺癌和淋巴瘤细胞系）酸化细胞外介质 [2]。

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Pantoprazole 在浓度高于200 µmol/L时，能提高小鼠EMT-6和人MCF-7癌细胞的内体pH值。此效应呈浓度依赖性，并在阿霉素存在下增强。[1]
用 pantoprazole (1 mmol/L) 预处理改变了阿霉素在MCF-7和EMT-6细胞内的分布，减少了阿霉素在细胞质点状区室（提示内体隔离）中的荧光，同时使其保留在细胞核内。[1]
流式细胞术分析显示，用 pantoprazole (1 mmol/L) 预处理显著增加了阿霉素在EMT-6细胞中的净摄取量，但在MCF-7细胞中减少了24%，在A431细胞中减少了36%。在较低浓度(100 µmol/L)下观察到类似趋势，但无统计学意义。[1]
用 pantoprazole (1 mmol/L) 预处理源自EMT-6和MCF-7细胞的多细胞层培养物，能显著增加阿霉素在组织中的穿透。在EMT-6 MCCs中穿透增加超过2倍，在MCF-7 MCCs中增加约1.3倍。荧光显微镜证实，在预处理的MCCs中，距离药物源较远的细胞阿霉素信号增强。[1]

在 MCF-7 异种移植物中，泮托拉唑钠水合物（BY1023 水合物钠；200 mg/kg；IP；每周一次，持续 3 周）和阿霉素的组合显着延长了肿瘤生长延迟 [1]。口服泮托拉唑钠水合物（0.3-3 mg/kg）以剂量依赖性方式减少急性瘘大鼠中美吡唑诱导的刺激性酸分泌和幽门结扎大鼠中的基础酸分泌[4]。

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在携带MCF-7异种移植瘤的小鼠中，于阿霉素给药前2小时使用 pantoprazole (200 mg/kg, 腹腔注射) 预处理，与单用阿霉素相比，导致肿瘤组织内阿霉素荧光信号显著增加，表明药物分布得到改善。定量分析显示，在 pantoprazole 预处理组中，阿霉素强度随功能血管距离增加而下降的梯度更平缓。此效应在EMT-6肿瘤中未观察到。[1]
在MCF-7异种移植瘤模型中，单次阿霉素(8 mg/kg, 静脉注射)给药前，使用单次剂量的 pantoprazole (200 mg/kg, 腹腔注射) 预处理，与单用阿霉素或对照组相比，能显著增加肿瘤生长延迟。单用 pantoprazole 对肿瘤生长无影响。[1]
在对阿霉素相对耐药的A431异种移植瘤中，单次阿霉素给药前使用 pantoprazole 预处理仅导致微小的、边缘显著性的生长延迟增加。然而，当与阿霉素联合每周给药一次、连续三周时，在该模型中没有观察到显著的生长延迟。[1]
在MCF-7异种移植瘤中，每周一次、连续三周于阿霉素(6 mg/kg, 静脉注射)给药前使用 pantoprazole (200 mg/kg, 腹腔注射) 预处理，与单次给药方案相比，导致了更显著的肿瘤生长延迟。[1]

在不同的体外试验系统中比较了H+/K（+）-ATP酶抑制剂泮托拉唑和奥美拉唑的作用。在导致胃膜囊泡内部酸化的条件下，泮托拉唑和奥美拉唑抑制H+/K（+）-ATP酶活性，IC50值分别为6.8和2.4微M。当通过加入咪唑（5 mM）（一种可渗透膜的弱碱）来减少脊髓内酸化时，奥美拉唑的抑制作用部分丧失（IC50 30 microM），泮托拉唑的抑制效果几乎完全丧失。在用泵膜囊泡孵育40分钟后，泮托拉唑和奥美拉唑浓度分别为1.1和0.6微M时，膀胱内H+浓度出现了最大的一半降低。同样，当通过加入咪唑（2.5 mM）降低了血管内H+浓度时，泮托拉唑（20和60微M）没有降低剩余的血管内质子浓度，而奥美拉唑（10和30微M）却降低了。这两种药物在pH 3.0时以相似的效力抑制木瓜蛋白酶活性，并以相似的时间依赖方式灭活酶；在pH 5.0时，奥美拉唑（IC50 17微M）比泮托拉唑（IC50 37微M）更有效，酶抑制速度比泮美拉唑快。这些结果表明，泮托拉唑在高酸性条件下是H+/K（+）-ATP酶的强效抑制剂，在pH 5.0等微酸性pH值下比奥美拉唑更稳定[3]。

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为测量内体pH，将EMT-6或MCF-7细胞与不同浓度的 pantoprazole（及其他对照药物）及一种可被内体摄取的pH敏感荧光葡聚糖偶联物(FITC/TMR-dextran)共同孵育3小时。随后在培养基中再孵育2小时，使用流式细胞仪测量荧光。利用已知pH缓冲液中的离子载体尼日利亚菌素对pH依赖型(FITC)与pH非依赖型(TMR)荧光比值进行校准，以确定内体pH。[1]
为评估阿霉素在细胞内的分布，将生长在腔室盖玻片上的细胞用 pantoprazole (1 mmol/L) 预处理2小时，然后与含阿霉素(2 µg/mL)的培养基孵育1小时。洗涤后，使用带有特定激发/发射滤光片的荧光显微镜观察细胞内阿霉素荧光。为观察内体，细胞用pH敏感染料LysoSensor Yellow/Blue共染色。[1]
为通过流式细胞术测量阿霉素的净细胞摄取量，细胞用生理盐水或 pantoprazole (1 mmol/L) 处理2小时，随后与阿霉素(1.8 µmol/L)孵育1小时。洗涤细胞后，使用配备530 nm发射滤光片的流式细胞仪测量平均阿霉素荧光强度。[1]
为在体外模拟肿瘤的环境中评估药物穿透，通过将EMT-6或MCF-7细胞在胶原包被的膜上生长6-8天来建立多细胞层培养物。MCCs用或不用 pantoprazole (1 mmol/L) 预处理2小时。将放射性标记的阿霉素(10 µmol/L，与琼脂糖混合以防止对流)加在MCCs一侧，监测其随时间穿透MCC进入接收室的量，通过液体闪烁计数法测量。使用非细胞穿透性示踪剂(³H-蔗糖)的穿透作为内参，以控制MCC厚度的差异。平行的MCCs暴露于阿霉素后，对其冰冻切片进行荧光显微镜成像，以可视化药物分布。[1]

用泮托拉唑处理小鼠EMT-6和人MCF-7细胞，使用荧光光谱评估内体pH值的变化，并使用流式细胞术评估阿霉素的摄取。在多层细胞培养（MCC）中评估了泮托拉唑对阿霉素组织穿透的影响。泮托拉唑（>200μmol/L）增加了细胞内的内体pH值，也增加了阿霉素的核摄取。泮托拉唑预处理增加了阿霉素在MCC中的组织渗透[1]。

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对于肿瘤生长延迟研究，使用携带皮下MCF-7或A431异种移植瘤的雌性无胸腺裸鼠（或携带EMT-6肿瘤的同系Balb/C小鼠）。当肿瘤直径达到5-8 mm时，将小鼠随机分组。Pantoprazole 以200 mg/kg的剂量腹腔注射，溶于0.9%生理盐水。阿霉素以8 mg/kg（单次剂量研究）或6 mg/kg（多次剂量研究）的剂量静脉注射。对于联合治疗，在阿霉素注射前2小时给予 pantoprazole 腹腔注射。定期测量肿瘤体积和体重直至实验终点。[1]
为研究肿瘤中的阿霉素分布，使用携带EMT-6或MCF-7肿瘤（平均直径8-12 mm）的小鼠。在便于荧光检测的高剂量阿霉素(25 mg/kg, 静脉注射)给药前2小时，给予小鼠 pantoprazole (200 mg/kg, 腹腔注射)或载体。为标记功能血管和缺氧区域，小鼠在处死前还分别接受了静脉注射DIOC7 (1 mg/kg)和腹腔注射EF5。阿霉素注射后10分钟处死小鼠，取出肿瘤，冷冻，切片，并通过荧光显微镜和免疫组化分析药物相对于血管的分布。[1]
对于毒性研究，小鼠分别接受100、150、200、250或300 mg/kg剂量的 pantoprazole (腹腔注射)，单独使用或在阿霉素(8 mg/kg, 静脉注射)前2小时使用。每隔一天监测体重。[1]
对于药代动力学分析，给予Balb/C小鼠单次腹腔注射剂量的 pantoprazole (200 mg/kg)。在不同时间点通过心脏穿刺采集血液，分离血浆，并使用经验证的HPLC-MS/MS方法测定 pantoprazole 浓度。[1]

Animal/Disease Models: Mice bearing MCF-7 or A431 xenografts [1]
Doses: 200 mg/kg
Route of Administration: IP; once weekly for 3 weeks; alone or in combination with doxorubicin (6 mg/kg iv) First 2 hour
Experimental Results: The growth delay of MCF-7 xenografts with doxorubicin was even greater compared to the single dose combination. A single dose of doxorubicin Dramatically increased tumor growth delay. alone had no effect on growth delay.

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For tumor growth delay studies, female athymic nude mice bearing subcutaneous MCF-7 or A431 xenografts (or syngeneic Balb/C mice bearing EMT-6 tumors) were used. When tumors reached 5-8 mm in diameter, mice were randomized into treatment groups. Pantoprazole was administered intraperitoneally (i.p.) at a dose of 200 mg/kg, dissolved in 0.9% saline. Doxorubicin was administered intravenously (i.v.) at a dose of 8 mg/kg (single-dose study) or 6 mg/kg (multiple-dose study). For combination therapy, pantoprazole was given i.p. 2 hours before doxorubicin injection. Tumor volumes and body weights were measured regularly until endpoints were reached. [1]
For studying doxorubicin distribution in tumors, mice bearing EMT-6 or MCF-7 tumors (8-12 mm mean diameter) were treated. They received pantoprazole (200 mg/kg, i.p.) or vehicle 2 hours before a high dose of doxorubicin (25 mg/kg, i.v.) to facilitate fluorescence detection. To mark functional vasculature and hypoxia, mice also received intravenous DIOC7 (1 mg/kg) and intraperitoneal EF5 respectively, shortly before sacrifice. Mice were sacrificed 10 minutes after doxorubicin injection, tumors were excised, frozen, sectioned, and analyzed by fluorescence microscopy and immunohistochemistry for drug distribution relative to blood vessels. [1]
For toxicity studies, mice were treated with pantoprazole at doses of 100, 150, 200, 250, or 300 mg/kg (i.p.), alone or 2 hours before doxorubicin (8 mg/kg, i.v.). Body weight was monitored every other day. [1]
For pharmacokinetic analysis, Balb/C mice were treated with a single i.p. dose of pantoprazole (200 mg/kg). Blood was collected via cardiac puncture at various time points, plasma was isolated, and pantoprazole concentration was determined using a validated HPLC-MS/MS method. [1]

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.

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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/

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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/

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Following a single intraperitoneal injection of pantoprazole (200 mg/kg) in mice, the peak plasma concentration was approximately 300 µmol/L, occurring within the first hour. [1]
The plasma concentration declined to about 150 µmol/L at 2 hours post-injection. [1]
By 5 hours post-injection, the plasma concentration had decreased to less than 1% of the peak concentration. [1]
At 24 hours post-injection, less than 0.01 µmol/L of pantoprazole was detectable in plasma. [1]

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).

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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.

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Protein Binding
Approximately 98%

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Interactions
Pantoprazole causes prolonged inhibition of gastric acid secretion, and thereby may interfere with the absorption of these medications /ampicillin or iron salts or ketoconazole/ and others for which bioavailability is determined by gastric pH. /Pantoprazole sodium/
Pantoprazole, although metabolized by hepatic cytochrome p450 systems, does not appear to either inhibit or induce cytochrome p450 enzyme activity. To date, no clinically significant interactions have been noted from such commonly used drugs as diazepam, phenytoin, nifedipine, theophylline, digoxin, warfarin, or oral contraceptives. /Pantoprazole sodium/
Pantoprazole, by increasing gastric pH, has the potential to affect the bioavailability of any medication for which absorption is pH-dependent. Also, pantoprazole may prevent the degradation of acid-labile drugs. /Pantoprazole sodium/
In other in vivo studies, ethanol, glyburide, caffeine, antipyrine, metronidazole, and amoxicillin, had no clinically relevant interactions with pantoprazole. /Pantoprazole sodium/

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In mice, the maximum tolerated dose of pantoprazole when combined with doxorubicin (8 mg/kg) was determined to be 200 mg/kg. At this dose, combined treatment caused a temporary decrease in body weight (approximately 15%) within the first 5-8 days, followed by recovery. [1]
At higher doses of pantoprazole (250 or 300 mg/kg) combined with doxorubicin, mice showed continual loss of body weight beyond 20 days. [1]
Treatment with pantoprazole alone (up to 300 mg/kg) or doxorubicin alone (8 mg/kg) resulted in minimal increase in body weight, similar to saline controls. [1]

[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.

Therapeutic Uses
Pantoprazole delayed-release tablets are indicated for the short-term (up to 8 weeks) treatment of heartburn and other symptoms associated with gastroesophageal reflux disease (GERD). Pantoprazole for injection is indicated for the short-term (7 to 10 days) treatment of GERD in patients who are unable to continue taking pantoprazole delayed-release tablets. Pantoprazole for injection is not indicated for initial treatment of GERD. /Included in US product labeling/ /Pantoprazole sodium/
Pantoprazole is indicated for the prevention of relapse in patients with reflux esophagitis. /NOT included in US product labeling/ /Pantoprazole sodium/
Pantoprazole is indicated for short-term (up to 4 weeks) treatment for symptom relief and healing in patients with active duodenal ulcer. /NOT included in US product labeling/ /Pantoprazole sodium/
Pantoprazole, in combination with clarithromycin and either amoxicillin or metronidazole, is indicated for treatment of patients with an active duodenal ulcer who are Helicobacter pylori positive. /NOT included in US product labeling/ /Pantoprazole sodium/
For more Therapeutic Uses (Complete) data for PANTOPRAZOLE (6 total), please visit the HSDB record page.

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Drug Warnings
Anaphylaxis has been reported with the use of IV pantoprazole sodium. Immediate medical intervention and drug discontinuance are required if anaphylaxis or other severe hypersensitivity reactions occurs. /Pantoprazole sodium/
Adverse effects occurring in more than 1% of patients receiving oral pantoprazole for up to 8 weeks and more frequently than in those receiving placebo include diarrhea and hyperglycemia. Adverse effects occurring in 1% or more of patients receiving oral pantoprazole for up to 12 months and more frequently than in those receiving ranitidine include headache, abdominal pain, and abnormal liver function test results. Adverse effects occurring in 4% or more of patients receiving IV pantoprazole and that were possibly, probably, or definitely related to treatment include abdominal pain, chest pain, rash, and pruritus. Adverse effects occurring in more than 1% of patients receiving IV pantoprazole and that generally had an unclear relationship to the drug include headache, injection site reaction, dyspepsia, diarrhea, vomiting, dizziness, and rhinitis. /Pantoprazole sodium/
There have been spontaneous reports of adverse events; angioedema (Quincke's edema); anterior ischemic optic neuropathy; severe dermatologic reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN, some fatal); hepatocellular damage leading to jantice and and hepatic failure; pancreatitis; pancytopenia; and rhabdomyolysis. In addition, also observed have been confusion, hypokinesia, speech disorder, increased salivation, vertigo, nausea, tinnitus, and blurred vision. /Pantoprazole sodium/
FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility./ /Pantoprazole sodium/
For more Drug Warnings (Complete) data for PANTOPRAZOLE (8 total), please visit the HSDB record page.

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Pharmacodynamics
This drug acts to decrease gastric acid secretion, which reduces stomach acidity. Pantoprazole administration leads to long-lasting inhibition of gastric acid secretion. **General Effects** Pantoprazole has been shown to reduce acid reflux-related symptoms, heal inflammation of the esophagus, and improve patient quality of life more effectively than histamine-2 receptor antagonists (H2 blockers). This drug has an excellent safety profile and a low incidence of drug interactions. It can be used safely in various high-risk patient populations, including the elderly and those with renal failure or moderate hepatic dysfunction. 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. **A note on laboratory testing abnormalities** During treatment with antisecretory medicinal products such as pantoprazole, serum gastrin (a peptide hormone that stimulates secretion of gastric acid) increases in response to the decreased acid secretion caused by proton pump inhibition. The increased gastrin level may interfere with investigations for neuroendocrine tumors. Published evidence suggests that proton pump inhibitors should be stopped 14 days before chromogranin A (CgA) measurements. This permits chromogranin A levels, that might be falsely elevated after proton pump inhibitor treatment, to return to the normal reference range. Reports have been made of false-positive results in urine screening tests for tetrahydrocannabinol (THC) in patients receiving the majority of proton pump inhibitors, including pantoprazole. A confirmatory method should be used.

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Pantoprazole is a proton pump inhibitor (PPI) that inhibits vacuolar H⁺-ATPase (V-H⁺-ATPase). In the context of this cancer research, it is investigated not for its anti-acid effects but as a modulator of the tumor microenvironment. By increasing the pH of acidic intracellular compartments (like endosomes and lysosomes), it can inhibit the sequestration of weakly basic chemotherapeutic drugs such as doxorubicin. This mechanism is proposed to increase the availability of the drug for its nuclear target and to enhance its distribution from blood vessels into deeper tumor tissue, potentially overcoming a mechanism of drug resistance related to poor drug penetration. [1]
The study concluded that pretreatment with pantoprazole could improve the therapeutic index of doxorubicin in some solid tumors by enhancing its distribution and cytotoxicity. The preclinical findings contributed to the initiation of clinical trials evaluating high-dose pantoprazole in combination with chemotherapy. [1]

2(C16H14F2N3NAO4S).3(H2O)

864.75

864.145

164579-32-2

Pantoprazole;102625-70-7;Pantoprazole sodium;138786-67-1;S-Pantoprazole sodium trihydrate;1416988-58-3

4679

Off-white solid

149-150
139-140 °C, decomposes
Mol wt: 405.36. White to off-white solid; mp: >130 °C (dec); UV max (methanol): 289 (E=1.64X10+4) /Sodium salt/

2.4

185Ų

1

9

7

26

490

0

VNKNFEINTHUQGZ-UHFFFAOYSA-N

InChI=1S/2C16H14F2N3O4S.2Na.3H2O/c2*1-23-13-5-6-19-12(14(13)24-2)8-26(22)16-20-10-4-3-9(25-15(17)18)7-11(10)21-16;;;;;/h2*3-7,15H,8H2,1-2H3;;;3*1H2/q2*-1;2*+1;;;

disodium;5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-ide;trihydrate

BY1023 sodium hydrate; SKF96022 sodium hydrate; BY1023; SKF96022; Protonix; BY 1023; BY-1023; SKF 96022; Pantoprazole sodium sesquihydrate; 164579-32-2; Protonix; Pantoprazole Sodium [USAN]; Somac Control; disodium;5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-ide;trihydrate; Pantoloc Control; SKF-96022

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~250 mg/mL (~578.21 mM)
DMSO : ~100 mg/mL (~231.28 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.78 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (5.78 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (5.78 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。