Retrospective Study Efficacy of pantoprazole plus perforation repair for peptic ulcer and its effect on the stress response

BACKGROUND Peptic ulcer(PU)is an abnormal phenomenon in which there is rupture of the mucosa of the digestive tract,which not only affects patients'normal life but also causes an economic burden due to its high medical costs.AIM To investigate the efficacy of pantoprazole(PPZ)plus perforation repair in patients with PU and its effect on the stress response.METHODS The study subjects were 108 PU patients admitted between July 2018 and July 2022,including 58 patients receiving PPZ plus perforation repair[research group(RG)]and 50 patients given simple perforation repair[control group(CG)].The efficacy,somatostatin(SS)concentration,stress reaction[malondialdehyde(MDA),lipid peroxide(LPO)],inflammatory indices[tumor necrosis factor(TNF)-α,C-reactive protein(CRP),interleukin(IL)-1β],recurrence,and complications(perforation,hemorrhage,and pyloric obstruction)were compared.RESULTS The overall response rate was higher in the RG than in the CG.Patients in the RG and IL-1β were significantly reduced to lower levels than those in the CG.Lower recurrence and complication rates were identified in the RG group.CONCLUSION Therefore,PPZ plus perforation repair is conducive to enhancing treatment outcomes in PU patients,reducing oxidative stress injury and excessive inflammatory reactions,and contributing to low recurrence and complication rates.

Prospects to the formation and control of potential dimer impurity E of pantoprazole sodium sesquihydrate

Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). The monographs of European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP) specify six impurities, viz.;impurities A, B, C, D, E and F, respectively for its active pharmaceutical ingredient (API). The identification and synthesis of all impurities except impurity E are well described in the literature;however, there is no report related to impurity E. The prospects to the formation and controlling of impurity E up to -0.03% in the synthesis of pantoprazole sodium sesquihydrate (PAN) were discussed in detail for the first time. The present work described the journey towards the successful development of an optimal preparation procedure of dimer impurity E. The most plausible mechanism involved in the formation of impurity E has been proposed.

Effects of omeprazole or pantoprazole on platelet function in non-ST-segment elevation acute coronary syndrome patients receiving clopidogrel

Background: This study evaluated the effect of omeprazole or pantoprazole on platelet reactivity in non-STsegment elevation acute coronary syndrome(NSTE-ACS) patients receiving clopidogrel.Methods: Consecutive patients with NSTE-ACS(n =620) from general hospital of Shenyang Military Command were randomized to the omeprazole or pantoprazole(20mg/d) group(1:1), and received routine dual antiplatelet treatment. Patients' reversion rate of adenosine diphosphate-induced platelet aggregation(ADP-PA) was assessed at baseline, 12 to 24 h after administration of medication, and after 72 h of percutaneous coronary intervention(PCI). The primary endpoint of the study was platelet reactivity assessed with ADP-PA at 30 days after PCI. Adverse events(AEs) were recorded for 30-day and 180-day follow-up periods.Results: There were no significant differences between both the groups in platelet response to clopidogrel at 12–24h after drug administration(54.09%±18.90% vs. 51.62%±19.85%, P=0.12), 72 h after PCI(52.15%±19.45% vs. 49.66%±20.05%, P=0.18), and 30 days after PCI(50.44%±14.54% vs. 48.52%±15.08%, P=0.17). The rate of AEs did not differ significantly between groups during the 30-day(15.2% vs. 14.8%, P=0.91) and 180-day(16.5% vs. 14.5%, P=0.50) follow-up periods after PCI.Conclusion: The addition of omeprazole or pantoprazole to clopidogrel did not restrict the effect of platelet aggregation by reducing the conversion of clopidogrel. Compared with clopidogrel alone, pantoprazole-clopidogrel and omeprazoleclopidogrel combinations did not increase the incidence of adverse clinical events during 30-day and 180-day follow-up periods after PCI.

质子泵抑制剂Lansoprazole和Pantoprazole的药理与临床

第一代质子泵抑制剂奥美拉唑(omepra-zole)以具有抑制H^+/K^+-ATP酶的独特作用,完全阻断任何刺激引起的胃酸分泌,强烈持久地抑制胃酸分泌,对常规疗法不能奏效的消化性溃疡和严重食管反流病的疗效明显优于数年来高居世界最畅销药物之首的雷尼替丁。自奥美拉唑1988年2月在瑞典上市以来,法、美等40多个国家已销售应用,1990年已跃为世界畅销的第35位药物。质子泵抑制剂已引起人们极大的关注。

Stability indicating high performance thin-layer chromatographic method for simultaneous estimation of pantoprazole sodium and itopride hydrochloride in combined dosage form

A specific, precise and stability indicating high-performance thin-layer chromatographic method for simultaneous estimation of pantoprazole sodium and itopride hydrochloride in pharmaceutical formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F254 as the stationary phase. The solvent system consisted of methanol：water：ammonium acetate; 4.0：1.0：0.5 （v/v/v）. This system was found to give compact and dense spots for both itopride hydrochloride （Rf value of 0.55__＋0.02） and pantoprazole sodium （Rf value of 0.85＋0.04）. Densitometric analysis of both drugs was carried out in the reflectance- absorbance mode at 289 nm. The linear regression analysis data for the calibration plots showed a good linear relationship with R2=0.9988___0.0012 in the concentration range of 100--400 ng for pantoprazole sodium. Also, the linear regression analysis data for the calibration plots showed a good linear relationship with R2=0.9990_＋0.0008 in the concentration range of 200-1200 ng for itopride hydrochloride. The method was validated for specificity, precision, robustness and recovery. Statistical analysis proves that the method is repeatable and selective for the estimation of both the said drugs. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating method.

Comparison of intravenous pantoprazole and ranitidine in patients with dyspepsia presented to the emergency department: a randomized, double blind, controlled trial

BACKGROUND:This study aimed to compare pantoprazole,a proton-pomp inhibitors(PPIs),and ranitidine,a H2 receptor antagonists(H2RA),in ceasing dyspeptic symptoms in the emergency department(ED).METHODS:This randomized,double-blinded study compared the effectiveness of 50 mg ranitidine(Ulcuran®)and 40 mg pantoprazole(Pantpas®),given in a 100 m L saline solution by an intravenous rapid infusion within 2–4 minutes in patients with dyspepsia presented to the ED.Pain intensity was measured at baseline,30 and 60 minutes after the drug administration.RESULTS:A total of 72 patients were eligible for the study.Of these patients,2 were excluded from the study because the initial visual analogue scale(VAS)scores were under 20 mm and 4 were excluded from the statistical analysis because of being diagnosed as having other causes of epigastric pain despite being allocated to one of the study groups.Thirty-three patients in the pantoprazole group and 33 patients in the ranitidine group were analyzed ultimately.The mean age of the patients was36.6±15 years,and 26(39.4%)patients were male.Both of the groups reduced pain effectively at 30[27.6±28(18 to 37)vs.28.3±23(20 to 37),respectively]and 60 minutes[39.6±39(26 to 53)vs.42.3±25(33 to 51),respectively].There were 13(39.4%)patients in the pantoprazole group and 8(24.2%)patients in the ranitidine group who required additional drug at the end of the study(P=0.186).CONCLUSION:Intravenous pantoprazole and ranitidine are not superior to each other in ceasing dyspeptic symptoms at 30 and 60 minutes in the ED.

The mechanism of combination with hemocoagulase and pantoprazole in upper gastrointestinal bleeding

Objective:Through the combination with hemocoagulase and pantoprazole on gastrointestinal bleeding, to observe the changes of serum BUN (blood urea nitrogen), LPO (LPO), NO (nitric oxide), TNF-α(TNF alpha), hs-CRP (high sensitivity C reactive protein) and cortisol levels, and to explore the mechanism of combination. Methods:110 cases of upper gastrointestinal bleeding in our hospital from January 2015 to September 2016 were selected and divided into the control group and the observation group, 55 cases for each group. Patients were treated with bed rest, fasting, intravenous nutrition, oxygen, and according to the individual situation actively supplement blood capacity, and the control group were treated with 40 mg intravenous pantoprazole treatment, 2 times/d;the patients in the observation group were treated with 2 kU hemocoagulase injection based on the treatment of control group, 2 times of intravenous injection per day, and all patients were treated for 3 d, and then the BUN, LPO, NO, TNF-α, hs-CRP and cortisol were detected. Results:(1) There were no significantly differences of the serum levels of BUN, LPO, and NO of the two groups before treatment (P>0.05). After treatment, the serum levels the two groups were significantly lower than before treatment, and LPO, BUN, and NO levels in the observation group were significantly better than the control group (P<0.05);(2) There were no significantly differences of the serum levels of TNF-α, hs-CRP, and cortisol of the two groups before treatment (P>0.05). After treatment, the serum levels in the two groups were significantly lower than before treatment, and TNF-α, hs-CRP, and cortisol levels in the observation group were significantly better than the control group (P<0.05). Conclusions:The treatment of patients with combined use of hemocoagulase and pantoprazole on gastrointestinal bleeding, can significantly improve the serum levels of BUN, LPO, NO, TNF-α, hs-CRP and cortisol levels, and further illustrates the synergistic effect of the combination, also shows that the combination of two drugs for patients with upper gastrointestinal bleeding can improve the symptoms of hemorrhage, reduce inflammation and stress, and improve the treatment effect.

Analysis of the Effect of Pantoprazole and Omeprazole on Pain Relief in Patients with Gastric Ulcer

Objective:To analyze the effect of pantoprazole and omeprazole in the treatment of patients with gastric ulcer.Methods:The treatment effect,recurrence rate,helicobacter pylori negative conversion rate,adverse reaction status and pain relief time of the two groups were compared.Results:The total effective rate of the experimental group(97.78%,44/45)was higher than that of the control group(84.44%,38/45),P<0.05;The recurrence rate(4.44%,2/45)and Helicobacter pylori negative conversion rate(95.56%,43/45)of the experimental group were significantly higher than those of the control group(P<0.05);The incidence of adverse reactions in the experimental group(11.11%,5/45)was lower than that in the control group(15.56%,7/45)(P>0.05);The pain relief time of the experimental group was(2.24±1.16)d,which was shorter than that of the control group(P<0.05).Conclusion:In the process of clinical treatment of gastric ulcer,pantoprazole has significant curative effect and low recurrence rate,which can eradicate Helicobacter pylori as soon as possible,shorten the pain time and make the treatment safer.

COMPARISON OF RANITIDINE AND PANTOPRAZOLE FOR STRESS ULCER BLEEDING PROPHYLAXIS IN CRITICALLY ILL PATIENTS REQUIRING MECHANICAL VENTILATION

Objective To compare the efficacy of Ranitidine and Pantoprazole for the prevention of haemorrhage from stress ulcer among critical care patients. Methods A total of 121 critically ill patients were included in this retrospective study. The choice of pharmacologic stress ulcer prophylaxis were either Ranitidine or Pantoprazole. The primary outcome was the incidence of stress-related significant upper gastrointestinal bleeding, and the secondary outcome was the incidence of hospital acquired pneumonia (HAP). Results A total of 63 patients were given Ranitidine, and 58 patients were given Pantoprazole for stress ulcer bleeding prophylaxis. Nine patients (7.44%, 9/121) developed clinically-important upper gastrointestinal bleeding, including 5 (7.94%, 5/63) in the Ranitidine group, and 4 (6.90%,4/58) in the Pantoprazole group. The rate of HAP was 3.17% (2/63) in the Ranitidine group, and 15.52% (9/58) in the Pantoprazole group. Conclusion Ranitidine was associated with lower rates of HAP as compared with Pantoprazole, with no statistically significant difference in clinically-important gastrointestinal hemorrhage. Because of limited trial data, future well-designed and powerful randomized, clinical trials are warranted.

埃索美拉唑钠预防咽喉肿瘤术后并发应激性溃疡出血的研究

我们对80例咽喉肿瘤术后患者分别采用埃索美拉唑和泮托拉唑进行应激性溃疡出血预防性治疗的对比研究。1资料与方法1.1一般资料。选择2011年2月～11月我科咽喉肿瘤患者80例,随机分为2组,治疗组40例,男36例,女4例,平均年龄57.2岁;对照组40例,男35例,女5例,平均年龄59.8岁。两组患者年龄、性别、病种、手术时间、吸烟史、饮酒史比较差异无明显差异。

Effect of low-dose amitriptyline on globus pharyngeus and its side effects

AIM:To compare the efficacy and side effects of lowdose amitriptyline(AMT)with proton pump inhibitor treatment in patients with globus pharyngeus.METHODS:Thirty-four patients who fulfilled the RomeⅢcriteria for functional esophageal disorders were included in this study.Patients were randomly assigned to receive either 25 mg AMT before bedtime(AMT group)or 40 mg Pantoprazole once daily for 4 wk(conventional group).The main efficacy endpoint was assessed using the Glasgow Edinburgh Throat Scale(GETS).The secondary efficacy endpoints included the Medical Outcomes Study 36-item short form health survey[social functioning(SF)-36]and the Pittsburgh Sleep Quality Index.Treatment response was defined as a>50%reduction in GETS scores.All patients entering this study recorded side effects at days 1,8,15,22 and 29 using a visual analogue scale.RESULTS:Thirty patients completed the study.After 4 wk of treatment,the AMT group had a greater response than the conventional group(75%vs 35.7%,P=0.004).At day 3,the AMT group showed significantly more improvement than the Conventional group in GETS score(3.69±1.14 vs 5.64±1.28,P=0.000).After 4 wk of treatment,the AMT group showed significantly greater improvement in GETS score and sleep quality than the Conventional group(1.25±1.84 vs 3.79±2.33,4.19±2.07 vs 8.5±4.97;P<0.01 for both).Additionally,the AMT group was more likely than the Conventional group to experience improvement in the SF-36,including general health,vitality,social functioning and mental health(P=0.044,0.024,0.049 and 0.005).Dry mouth,sleepiness,dizziness and constipation were the most common side effects.CONCLUSION:Low-dose AMT is well tolerated and can significantly improve patient symptoms,sleep and quality of life.Thus,low-dose AMT may be an effective treatment for globus pharyngeus.

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk.

Impact of Nicotine Consumption on Hyper Acidic Patients Taking PPI: An <i>In-Vitro</i>and Computational Analysis

The study aims to investigate the protein binding kinetics of nicotine and a PPI (pantoprazole) with Bovine Serum Albumin (BSA) through UV spectroscopy and computational modeling. Data was obtained by using nicotine and pantoprazole and warfarin and diazepam as the two site specific probes on Bovine serum albumin (BSA). In-vitro and in-silico modeling was carried out in creating an environment that simulates the body environment. Cellulose membrane tubes were cut into 9 cm and tied tightly not to let any mixtures leak out. To determine number of binding sites, association constants by using Scatchard plot, predominant binding site of each drug and rise in % of free fraction of one by the other were analyzed using equilibrium dialysis method. Molecular docking further verifies the observations. In Scatchard plot analysis, for nicotine, n1, n2, k1 and k2 = 2.2, 7.6, 0.18 μM&minus;1 and 0.02 μM&minus;1 and for pantoprazole, n1, n2, k1?and k2 = 0.42, 1.2, 0.40 μM&minus;1 and 0.03 μM&minus;1. Nicotine binds more to diazepam site (site-II) and pantoprazole mainly to warfarin site (site-I). In molecular docking, the binding affinity of nicotine being &minus;5.7 kcal/mole demonstrates higher affinity for site-II than that of pantoprazole whose binding affinity is &minus;8.0 kcal/mole. In absence and presence of warfarin, the free fraction of pantoprazole bound to BSA (1:1) was increased from 37.79% to 82.44% and 51.78% to 98.80% respectively by nicotine. On the other hand, free fraction of nicotine was raised by pantoprazole from 12.89% to 75.70% and 50.08% to 99.66% in the absence and presence of diazepam. Both the results of spectroscopic and computational molecular docking suggest that administering pantoprazole with nicotine might increase the % free fraction of pantoprazole more. Thus, nicotine consumption can be beneficial for smoker people taking PPI like pantoprazole.