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Cureus Jan 2020Introduction Perforation, obstruction, and bleeding remain the most frequently encountered complications of peptic ulcer disease (PUD). Bleeding may be in the form of...
Introduction Perforation, obstruction, and bleeding remain the most frequently encountered complications of peptic ulcer disease (PUD). Bleeding may be in the form of hematemesis or melena. The treatment of choice in patients with a bleeding peptic ulcer is endoscopic ligation to maintain the hemostatic balance followed by the administration of proton pump inhibitors (PPIs). This study focuses on the evaluation and comparison of intravenous (IV) and oral PPIs in terms of prevention of re-bleeding after successful endoscopy for peptic ulcers. Methods A prospective, comparative study was conducted in a tertiary care hospital in Pakistan from January 1, 2018 to June 30, 2019. The trial included known cases of PUD admitted with active upper gastrointestinal bleeding (UGIB). They were randomly divided into two groups: one received oral pantoprazole and the other was administered IV pantoprazole. The outcomes for both groups were compared. Data was entered and analyzed using Statistical Package for the Social Sciences (SPSS) software version 23.0 (IBM, Armonk, NY) Results There were 96 (48%) patients in the IV pantoprazole group and 104 (52%) in the oral group. From 24 hours after the medication onwards, the IV pantoprazole group showed a significant improvement in hemoglobin (Hb) levels (p: 0.01); the group also showed improvement in supine systolic BP at 48 hours (p: 0.04) and in diastolic BP at both 12 and 48 hours as compared to the oral pantoprazole group (p: 0.05). The mean duration of hospital stay, need for blood transfusion and repeat endoscopy, re-bleeding, and mortality rates were similar for both groups (p: >0.05). Conclusion We could not find any statistically significant difference between oral and IV routes of pantoprazole administration in the prevention of rebleeding when used after successful therapeutic endoscopy in patients with bleeding PUDs.
PubMed: 32133263
DOI: 10.7759/cureus.6741 -
Iranian Journal of Basic Medical... 2024Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin...
OBJECTIVES
Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin analog that inhibits the secretion of many hormones such as gastrin. This study aimed to assess the effects of pantoprazole on the bone when used with octreotide in an animal model.
MATERIALS AND METHODS
Forty-eight male Wistar rats were randomly assigned into 4 groups: A) pantoprazole 3 mg/Kg/day orally; B) Sandostatin LAR 1 mg/month intramuscular injection; C) Pantoprazole and Sandostatin LAR; and D) Control group. After 90 days of the experiment, bone densitometry was done and serum and urine samples were collected for analysis.
RESULTS
The results indicated a significant decrease in the global, spine, femur, and tibia bone mineral density (BMD) and bone mineral content (BMC) in the pantoprazole group compared to the control group (<0.05). There was a significant increase in the levels of PTH, gastrin, and alkaline phosphatase (ALP) in the pantoprazole group compared to the control group (<0.05). There was no significant difference in the serum levels of gastrin, PTH, ALP, and also BMD in the rats that received sandostatin+ pantoprazole or sandostatin alone, compared to the control group.
CONCLUSION
This study showed that the pantoprazole-induced bone loss, through elevation of serum gastrin and PTH, was preventable by concomitant use of a long-acting somatostatin analog.
PubMed: 38234669
DOI: 10.22038/IJBMS.2023.71245.15571 -
Anesthesia and Analgesia Nov 2022Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical settings but has not been broadly evaluated during perioperative care.
METHODS
The Implementation of Pharmacogenomic Decision Support in Surgery (ImPreSS) Trial is a prospective, single-center study consisting of a prerandomization pilot and a subsequent randomized phase. We describe findings from the pilot period. Patients planning elective surgeries were genotyped with pharmacogenomic results, and decision support was made available to anesthesia providers in advance of surgery. Pharmacogenomic result access and prescribing records were analyzed. Surveys (Likert-scale) were administered to providers to understand utilization barriers.
RESULTS
Of eligible anesthesiology providers, 166 of 211 (79%) enrolled. A total of 71 patients underwent genotyping and surgery (median, 62 years; 55% female; average American Society of Anesthesiologists (ASA) score, 2.6; 58 inpatients and 13 ambulatories). No patients required postoperative intensive care or pain consultations. At least 1 provider accessed pharmacogenomic results before or during 41 of 71 surgeries (58%). Faculty were more likely to access results (78%) compared to house staff (41%; P = .003) and midlevel practitioners (15%) ( P < .0001). Notably, all administered intraoperative medications had favorable genomic results with the exception of succinylcholine administration to 1 patient with genomically increased risk for prolonged apnea (without adverse outcome). Considering composite prescribing in preoperative, recovery, throughout hospitalization, and at discharge, each patient was prescribed a median of 35 (range 15-83) total medications, 7 (range 1-22) of which had annotated pharmacogenomic results. Of 2371 prescribing events, 5 genomically high-risk medications were administered (all tramadol or omeprazole; with 2 of 5 pharmacogenomic results accessed), and 100 genomically cautionary mediations were administered (hydralazine, oxycodone, and pantoprazole; 61% rate of accessing results). Providers reported that although results were generally easy to access and understand, the most common reason for not considering results was because remembering to access pharmacogenomic information was not yet a part of their normal clinical workflow.
CONCLUSIONS
Our pilot data for result access rates suggest interest in pharmacogenomics by anesthesia providers, even if opportunities to alter prescribing in response to high-risk genotypes were infrequent. This pilot phase has also uncovered unique considerations for implementing pharmacogenomic information in the perioperative care setting, and new strategies including adding the involvement of surgery teams, targeting patients likely to need intensive care and dedicated pain care, and embedding pharmacists within rounding models will be incorporated in the follow-on randomized phase to increase engagement and likelihood of affecting prescribing decisions and clinical outcomes.
Topics: Humans; Female; Male; Pharmacogenetics; Prospective Studies; Oxycodone; Pantoprazole; Tramadol; Succinylcholine; Perioperative Care; Pain; Hydralazine; Omeprazole
PubMed: 35213469
DOI: 10.1213/ANE.0000000000005951 -
Inflammopharmacology Jun 2024Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the...
Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.
Topics: Animals; Oxidative Stress; Stomach Ulcer; Rats; Apoptosis; Pantoprazole; Inflammation; Mesenchymal Stem Cells; Male; Mesenchymal Stem Cell Transplantation; Rats, Wistar; Anti-Ulcer Agents; Adipose Tissue; Combined Modality Therapy
PubMed: 38652367
DOI: 10.1007/s10787-024-01469-0 -
Acta Pharmacologica Sinica Nov 2021Liver fibrosis is one of the most severe pathologic consequences of chronic liver diseases, and effective therapeutic strategies are urgently needed. Proton pump...
Liver fibrosis is one of the most severe pathologic consequences of chronic liver diseases, and effective therapeutic strategies are urgently needed. Proton pump inhibitors (PPIs) are H/K-ATPase inhibitors and currently used to treat acid-related diseases such as gastric ulcers, which have shown other therapeutic effects in addition to inhibiting acid secretion. However, few studies have focused on PPIs from the perspective of inhibiting hepatic fibrosis. In the present study, we investigated the effects of pantoprazole (PPZ), a PPI, against liver fibrosis in a bile duct ligation (BDL) rat model, human hepatic stellate cell (HSC) line LX-2 and mouse primary HSCs (pHSCs), and explored the potential mechanisms underlying the effects of PPZ in vitro and in vivo. In BDL rats, administration of PPZ (150 mg· kg· d, i.p. for 14 d) significantly attenuated liver histopathological injury, collagen accumulation, and inflammatory responses, and suppressed fibrogenesis-associated gene expression including Col1a1, Acta2, Tgfβ1, and Mmp-2. In LX-2 cells and mouse pHSCs, PPZ (100-300 μM) dose-dependently suppressed the levels of fibrogenic markers. We conducted transcriptome analysis and subsequent validation in PPZ-treated LX-2 cells, and revealed that PPZ inhibited the expression of Yes-associated protein (YAP) and its downstream targets such as CTGF, ID1, survivin, CYR61, and GLI2. Using YAP overexpression and silencing, we demonstrated that PPZ downregulated hepatic fibrogenic gene expression via YAP. Furthermore, we showed that PPZ promoted the proteasome-dependent degradation and ubiquitination of YAP, thus inhibiting HSC activation. Additionally, we showed that PPZ destabilized YAP by disrupting the interaction between a deubiquitinating enzyme OTUB2 and YAP, and subsequently blocked the progression of hepatic fibrosis.
Topics: Animals; Bile Ducts; Gene Expression Profiling; HEK293 Cells; Hepatic Stellate Cells; Humans; Ligation; Liver Cirrhosis; Male; Pantoprazole; Proteolysis; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; YAP-Signaling Proteins
PubMed: 34465912
DOI: 10.1038/s41401-021-00754-w -
The Journal of Pediatrics Feb 2018To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient... (Clinical Trial)
Clinical Trial
OBJECTIVE
To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population that is traditionally excluded from clinical trials.
STUDY DESIGN
A total of 41 obese children (6-17 years of age), genotyped for CYP2C19 variants *2, *3, *4, and *17, received a single oral dose of pantoprazole, ~1.2 mg/kg lean body weight (LBW), with LBW calculated via a validated formula. Ten post-dose pantoprazole plasma concentrations were measured, and PK variables generated via noncompartmental methods (WinNonlin). Linear and nonlinear regression analyses and analyses of variance were used to explore obesity, age, and CYP2C19 genotype contribution to pantoprazole PK. PK variables of interest were compared with historic nonobese peers treated with pantoprazole.
RESULTS
Independent of genotype, when normalized to dose per kg total body weight, pantoprazole apparent clearance and apparent volume of distribution were significantly lower (P < .05) and systemic exposure significantly higher (P < .01) in obese vs nonobese children. When normalized per kg LBW, these differences were not evident in children ≥12 years of age and markedly reduced in children <12 years of age.
CONCLUSIONS
LBW dosing of pantoprazole led to pantoprazole PK similar to nonobese peers. Additional factors, other than body size (eg, age-related changes in CYP2C19 activity), appear to affect pantoprazole PK in children <12 years of age.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02186652.
Topics: Administration, Oral; Adolescent; Area Under Curve; Body Weight; Child; Cytochrome P-450 CYP2C19; Drug Dosage Calculations; Female; Gastroesophageal Reflux; Genotype; Humans; Male; Pantoprazole; Pediatric Obesity; Prospective Studies; Proton Pump Inhibitors
PubMed: 29389444
DOI: 10.1016/j.jpeds.2017.10.011 -
Journal of Physiology and Pharmacology... Dec 2021Surgically perforated stomach (since direct injury in rats until persisting defect and huge adhesions (day 1, day 7)) fairly represent an unresolved cytoprotection...
Novel insight into Robert's cytoprotection: complex therapeutic effect of cytoprotective pentadecapeptide pentadecapeptide BPC 157 in rats with perforated stomach throughout modulation of nitric oxide-system. Comparison with L-arginine, ranitidine and pantoprazole therapy and L-N-nitro-L-arginine...
Surgically perforated stomach (since direct injury in rats until persisting defect and huge adhesions (day 1, day 7)) fairly represent an unresolved cytoprotection issue, and thereby, we focused resolving of the immediate triad, particular vascular failure (vessels 'disappear'/empty), prolonged bleeding, debilitated defect large widening. Agents (mg/kg) or saline (controls) were given at 1 min post-injury as an abdominal bath (10 ml/rat throughout 2 min). Within 1 - 15 min post-injury period, with cytoprotective BPC 157 (0.01 μg), the rapidly restored vessels 'run' (vessels filled/reappeared) toward the perforated defect, and there is less bleeding, and defect contraction; advanced perforated lesion healing (day 1) to complete healing (day 7), and less adhesions. With pantoprazole (10 mg), early (vessels (worsening), bleeding (prolongation), defect (attenuated widening)) effect means eventual lesions and adhesions severity as in controls. Ranitidine (10 mg) early effect (vessels (improvement), bleeding (less bleeding), defect (eliminated widening, defect not changed)) means final lesions attenuation, but not complete healing, less adhesions. L-NAME (5 mg) early (vessels worsening, less bleeding, attenuated defect widening) and final (lesions aggravation, more adhesions) effect, versus L-arginine (100 mg) early (vessels improvement, more bleeding, attenuated defect widening) and final (lesions attenuation, less adhesions) effect, combined few simultaneously occurring nitric oxide (NO)-system distinct processes. Finally, in the stomach tissue surrounding defect, increased malondialdehyde (MDA)- and decreased NO-values, BPC 157 reversed to the normal healthy values, and mRNA expression studies (Cox2, VEGFa, Nos1, Nos 2, Nos3, Nkap (NF-kappa-B-activating protein gene)), done at that very early post-perforation-time, indicate a way how BPC 157 may act beneficially in the perforated stomach lesion throughout NO- and prostaglandinds-system.
Topics: Animals; Arginine; Cytoprotection; Hemorrhage; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pantoprazole; Peptide Fragments; Proteins; Ranitidine; Rats; Rats, Wistar; Stomach Diseases
PubMed: 35485358
DOI: 10.26402/jpp.2021.6.11 -
Molecules (Basel, Switzerland) Feb 2022Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain...
Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI). One-hundred-and-twenty-eight healthy male Wistar albino rats were included. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were assessed. ELISA was used to estimate the pro-inflammatory cytokines. The expression of and genes was assessed by quantitative real-time PCR. ERK1/2, JNK1/2, p38, cleaved caspase-3, and NF-κB proteins expressions were estimated using western blot assay. The kidneys were also histopathologically studied. The IRI resulted in impaired cellular functions with increased creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, and IL-1β serum levels, and up-regulated NF-ĸB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it down-regulated the expression of the gene and upregulated the gene. The treatment with vincamine, in addition to pantoprazole multiple doses, significantly alleviated the biochemical and histopathological changes more than pantoprazole or vincamine alone, whether the dose is single or multiple, declaring their synergistic effect. In conclusion, vincamine with pantoprazole multiple doses mitigated the renal IRI through the inhibition of apoptosis, attenuation of the extracellular signaling pathways through proinflammatory cytokines' levels, and suppression of the MAPK (ERK1/2, JNK, p38)-NF-κB intracellular signaling pathway.
Topics: Animals; Apoptosis; Biomarkers; Biopsy; Cytokines; Disease Management; Disease Models, Animal; Disease Susceptibility; Immunohistochemistry; Inflammation Mediators; Kidney Diseases; MAP Kinase Signaling System; Male; Pantoprazole; Rats; Reperfusion Injury; Vincamine
PubMed: 35209172
DOI: 10.3390/molecules27041383 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Mar 2017To study the characteristics and stability of new S(-) pantoprazole sodium hydrates. The X-ray single crystal diffractometer (SXRD), X-ray powder diffractometer...
To study the characteristics and stability of new S(-) pantoprazole sodium hydrates. The X-ray single crystal diffractometer (SXRD), X-ray powder diffractometer (PXRD), thermogravimetric analysis (TG) and infrared spectrometry (IR) were used to characterize S(-) pantoprazole sodium hydrates. The stability of the hydrates was evaluated by high temperature test,affecting factors test and accelerated test. The crystalline water in S(-) pantoprazole sodium hydrates were very easy to lose and obtain, but crystal structure was not changed significantly. The transition from S(-) pantoprazole sodium trihydrate to S(-) pantoprazole sodium hemipentahydrate occurred at approximately 40 ℃ and reversible transitions from hemipentahydrate to trihydrate occurred at high humidity. Two hydrates had no significant difference in accelerated test. The crystal structure of the two hydrates are almost the same, hemipentahydrate is more stable than trihydrates at high temperature or at exposure to light(at 4500 ± 500 lx).
Topics: Crystallization; Hot Temperature; Humidity; Pantoprazole; Water; X-Ray Diffraction
PubMed: 28752707
DOI: 10.3785/j.issn.1008-9292.2017.04.07 -
Journal of Neurogastroenterology and... Apr 2021S-isomer (S) pantoprazole is more bioavailable and less dependent on cytochrome 2C19 than is racemic pantoprazole. We aim to evaluate the efficacy and safety of 10 mg...
BACKGROUND/AIMS
S-isomer (S) pantoprazole is more bioavailable and less dependent on cytochrome 2C19 than is racemic pantoprazole. We aim to evaluate the efficacy and safety of 10 mg S-pantoprazole for treatment of non-erosive reflux disease (NERD).
METHODS
In this phase 3, double-blind, randomized placebo controlled, multicenter study, 174 NERD patients were randomized to one of both treatment groups: 10 mg S-pantoprazole, or placebo once daily for 4 weeks. Symptoms and safety were assessed. The efficacy endpoints were complete relief of symptoms, > 50% improvement of all reflux symptoms and recurrence.
RESULTS
Eighty-eight patients were assigned to the S-pantoprazole group (25 males, mean 43.7 years old) and 86 to the placebo group (32 males, mean 43.0 years old), and 163 patients were subjected to full Analysis Set. A higher proportion of patients in the S-pantoprazole group had complete symptom relief (42.0 % [34/81] vs 17.1% [14/82], < 0.001) and > 50% symptom responses (66.0% vs 50.0%, = 0.010 for heartburn; 64.2% vs 28.0%, = 0.010 for acid regurgitation; and 51.9% vs 30.5%, = 0.03 for epigastric discomfort) compared to the placebo group. The factors associated with poor responsiveness to PPI were older age, female, greater body mass index, and severe baseline symptoms.
CONCLUSIONS
Low dose of S-pantoprazole (10 mg) for 4 weeks was more efficacious than placebo in providing reflux symptom relief in patients with NERD, especially acid regurgitation. More doses or longer periods of treatment with S-pantoprazole would be needed to completely eliminate symptoms.
PubMed: 33795542
DOI: 10.5056/jnm19053