-
Veterinary Journal (London, England :... May 2024Abomasal ulcers are a significant concern in intensive animal farming due to their impact on animal health and productivity. While proton pump inhibitors (PPIs) such as...
Abomasal ulcers are a significant concern in intensive animal farming due to their impact on animal health and productivity. While proton pump inhibitors (PPIs) such as pantoprazole (PTZ) show promise in treating these ulcers, data on PTZ's pharmacokinetics (PK) in adult goats and sheep are limited. This study aims to fill this gap by investigating and comparing PTZ's PK in these species following single intravenous (IV) and subcutaneous (SC) administrations. Five healthy male goats and sheep were included in the study. PTZ concentrations in plasma samples were determined using a validated analytical method. Non-compartmental analysis was conducted, and statistical comparisons were made between IV and SC administrations and between species. Sheep and goats showed similar systemic exposure levels regardless of the administration route. However, sheep had a shorter t1/2 due to a higher V compared to goats. Cl values were comparable in both species, with low extraction ratio values. There were no significant differences in C and T between the two species with regards to SC administration, and complete bioavailability was observed. The MAT exceeded the t1/2 in both species, indicating a potential flip-flop phenomenon. Considering the AUC as a predictor for drug efficacy, and observing no significant differences in systemic exposure between sheep and goats for any route of administration, dosage adjustment between the two species may not be necessary. In field settings, SC administration proves more practical, providing not only complete bioavailability but also a longer half-life compared to IV. Further studies are warranted to explore the PK/PD of PTZ in small ruminants with abomasal ulcers, to fully comprehend its therapeutic efficacy in such scenarios.
PubMed: 38761957
DOI: 10.1016/j.tvjl.2024.106138 -
European Journal of Case Reports in... 2023Pantoprazole is one of the most widely used proton pump inhibitors, but anaphylaxis occurs rarely during its use. The purpose of reporting these two cases is to show...
INTRODUCTION
Pantoprazole is one of the most widely used proton pump inhibitors, but anaphylaxis occurs rarely during its use. The purpose of reporting these two cases is to show that pantoprazole is not a drug without problems; it can also cause anaphylactic reactions.
CASES DESCRIPTION
A 42-year-old woman presented to the emergency department due to dyspeptic complaints. Immediately at the end of the infusion of pantoprazole, there started to be numbness of the tongue, itching all over the body, and difficulty in breathing. Half an hour after taking a pantoprazole 40 mg capsule, a 58-year-old woman started to experience redness of the face, thickening of the tongue, itching, bloating, and dizziness. Arterial pressure was 80/60 mmHg, pulse 150/minute, while saturation had dropped to 88%. In both cases, fluids, adrenaline, antihistamines, methylprednisolone, and calcium were immediately started. After the improvement of their general conditions, both patients were discharged home.
DISCUSSION
The first case relates to anaphylaxis after the intravenous administration of pantoprazole, and the second case relates to the appearance of anaphylaxis after its oral administration.
CONCLUSION
Health workers need to be informed about the possibility of anaphylaxis in patients taking both oral and parenteral pantoprazole.
LEARNING POINTS
PPIs are generally safe, with a low percentage of side effects of 1-3%.Although hypersensitive reactions to PPIs are rare, cases of anaphylactoid reactions have also been reported in the literature.Anaphylaxis caused by taking pantoprazole should be considered in the differential diagnosis of anaphylaxis in both oral and parenteral administration of the drug.Doctors and pharmacists should be very careful when prescribing pantoprazole and other PPIs, especially to the elderly.
PubMed: 37680781
DOI: 10.12890/2023_004017 -
JGH Open : An Open Access Journal of... Feb 2024Combining proton pump inhibitors (PPIs) with prokinetics can provide synergistic action in patients with gastroesophageal reflux disease (GERD) and overlapping...
Efficacy and safety of pantoprazole and itopride in patients with overlap of gastroesophageal reflux disease and dyspepsia: A prospective, open-label, single-arm pilot study.
BACKGROUND AND AIM
Combining proton pump inhibitors (PPIs) with prokinetics can provide synergistic action in patients with gastroesophageal reflux disease (GERD) and overlapping dyspepsia, but data regarding this is lacking.
METHODS
This single-center, prospective study evaluated the efficacy and safety of 6-week treatment with fixed-drug combination (FDC) of pantoprazole (PPI) and itopride (prokinetic) in 50 patients with ≥3 month history of GERD and overlapping dyspepsia refractory to pantoprazole. Efficacy was assessed as reduction in GERD symptom assessment scale (GSAS) distress score for 15 symptoms from baseline to week 6. Adverse events (AEs) were monitored up to week 6.
RESULTS
Although heartburn was the most common symptom at week 6 (26.8%), its frequency significantly decreased from baseline (84.0%; <0.01). A similar trend was observed for other symptoms: pressure/discomfort inside chest (19.5%), belching (14.6%), regurgitation (12.2%), bloating (9.8%), flatulence (9.8%), early satiety (7.3%), acidic/sour taste in mouth (7.3%), nausea (7.3%), frequent gurgling in stomach/belly (4.9%), and pressure/lump in throat (2.4%). Mean distress scores of all symptoms markedly decreased at week 6. Three AEs ( = 2) of moderate intensity were reported.
CONCLUSION
The FDC of pantoprazole and itopride showed favorable efficacy and safety in patients with GERD and overlapping dyspepsia refractory to pantoprazole monotherapy. Nevertheless, further studies are warranted.
PubMed: 38344252
DOI: 10.1002/jgh3.12988 -
Pharmacogenomics and Personalized... 2023Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology... (Review)
Review
Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of prior to prescribing PPIs. There are strong data to support the influence of genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.
PubMed: 37383676
DOI: 10.2147/PGPM.S371994 -
Frontiers in Pharmacology 2023Pharmacogenetics-informed drug prescribing is increasingly applied in clinical practice. Typically, drug metabolizing phenotypes are determined based on genetic test...
Pharmacogenetics-informed drug prescribing is increasingly applied in clinical practice. Typically, drug metabolizing phenotypes are determined based on genetic test results, whereupon dosage or drugs are adjusted. Drug-drug-interactions (DDIs) caused by concomitant medication can however cause mismatches between predicted and observed phenotypes (phenoconversion). Here we investigated the impact of genotype on the outcome of CYP2C19-dependent DDIs in human liver microsomes. Liver samples from 40 patients were included, and genotyped for *2, *3 and *17 variants. S-mephenytoin metabolism in microsomal fractions was used as proxy for CYP2C19 activity, and concordance between genotype-predicted and observed CYP2C19 phenotype was examined. Individual microsomes were subsequently co-exposed to fluvoxamine, voriconazole, omeprazole or pantoprazole to simulate DDIs. Maximal CYP2C19 activity (V) in genotype-predicted intermediate metabolizers (IMs; *1/*2 or *2/*17), rapid metabolizers (RMs; *1/*17) and ultrarapid metabolizers (UMs; *17/*17) was not different from V of predicted normal metabolizers (NMs; *1/*1). Conversely, *2/*2 genotyped-donors exhibited V rates ∼9% of NMs, confirming the genotype-predicted poor metabolizer (PM) phenotype. Categorizing CYP2C19 activity, we found a 40% concordance between genetically-predicted CYP2C19 phenotypes and measured phenotypes, indicating substantial phenoconversion. Eight patients (20%) exhibited CYP2C19 IM/PM phenotypes that were not predicted by their CYP2C19 genotype, of which six could be linked to the presence of diabetes or liver disease. In subsequent DDI experiments, CYP2C19 activity was inhibited by omeprazole (-37% ± 8%), voriconazole (-59% ± 4%) and fluvoxamine (-85% ± 2%), but not by pantoprazole (-2 ± 4%). The strength of CYP2C19 inhibitors remained unaffected by genotype, as similar percental declines in CYP2C19 activity and comparable metabolism-dependent inhibitory constants (K/K) of omeprazole were observed between CYP2C19 genotypes. However, the consequences of CYP2C19 inhibitor-mediated phenoconversion were different between genotypes. In example, voriconazole converted 50% of *1/*1 donors to a IM/PM phenotype, but only 14% of *1/*17 donors. Fluvoxamine converted all donors to phenotypic IMs/PMs, but *1/*17 (14%) were less likely to become PMs than *1/*1 (50%) or *1/*2 and *2/*17 (57%). This study suggests that the differential outcome of CYP2C19-mediated DDIs between genotypes are primarily dictated by basal CYP2C19 activity, that may in part be predicted by genotype but likely also depends on disease-related factors.
PubMed: 37361233
DOI: 10.3389/fphar.2023.1201906 -
Cureus Jan 2024Globally, over 25% of the population suffers from acid-related disorders such as dyspepsia or gastroesophageal reflux disease (GERD), and around 7.6% of Indians report... (Review)
Review
Globally, over 25% of the population suffers from acid-related disorders such as dyspepsia or gastroesophageal reflux disease (GERD), and around 7.6% of Indians report having GERD symptoms on a frequent enough basis to warrant a diagnosis. Over the past three decades, proton-pump inhibitors (PPIs) have been the mainstay of medical therapy for acid-peptic diseases like GERD, etc. Additionally, they are frequently prescribed for prophylactic purposes and in conjunction with non-steroidal anti-inflammatory drugs. PPIs are generally prescribed for four to eight weeks. However, it may be prescribed for patients with comorbidities and multiple medications for a longer period of time. While this remains true in terms of effectiveness, concerns have been raised about the safety of long-term PPI use and the serious adverse effects that may result. Some of the observational and population-based cohort studies have shown an association between long-term use of PPIs and an increased risk of pneumonia, major cardiovascular events, dementia, vitamin B12 deficiency, bone fractures, gastric cancer, and kidney injury, among others. This review analyzes the clinical data supporting the long-term use of PPIs and takes a deep dive into whether these several emerging long-term concerns apply to the currently available PPIs in India. We have summarized a vast array of studies, including randomized trials, cohort studies, and meta-analyses, that report low or high incidences of major health risks linked with PPIs and have assessed their appropriateness over a given period.
PubMed: 38389608
DOI: 10.7759/cureus.52773 -
International Journal of General... 2023Until now, there is little evidence regarding clinical efficacy of 14-day vonoprazan-based bismuth quadruple therapy (BQT) for () eradication.
BACKGROUND
Until now, there is little evidence regarding clinical efficacy of 14-day vonoprazan-based bismuth quadruple therapy (BQT) for () eradication.
METHODS
Overall, 65 treatment-naïve patients with H. pylori infection who received 14-day vonoprazan-based BQT regimen (VBCA, n=17) or pantoprazole-based BQT regimen (PBCA, n=48) for H. pylori eradication were retrospectively included.
RESULTS
Neither successful H. pylori eradication (88.2% versus 91.7%, p=1.000) nor adverse event (52.9% versus 64.6%, p=0.397) was significantly different between VBCA and PBCA groups.
CONCLUSION
Vonoprazan seems to be as effective and safe as pantoprazole during a 14-day BQT regimen in treatment-naïve patients with infection.
PubMed: 37750104
DOI: 10.2147/IJGM.S427450 -
Journal of Clinical Medicine Mar 2024Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently,... (Review)
Review
Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.
PubMed: 38610738
DOI: 10.3390/jcm13071970 -
Nature Communications Dec 2023Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect...
Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect estimation remains a main challenge. Although various approaches have been proposed for this challenge, a systematic evaluation is still lacking. Here we emulated trials for thousands of medications from two large-scale real-world data warehouses, covering over 10 years of clinical records for over 170 million patients, aiming to identify new indications of approved drugs for Alzheimer's disease. We assessed different propensity score models under the inverse probability of treatment weighting framework and suggested a model selection strategy for improved baseline covariate balancing. We also found that the deep learning-based propensity score model did not necessarily outperform logistic regression-based methods in covariate balancing. Finally, we highlighted five top-ranked drugs (pantoprazole, gabapentin, atorvastatin, fluticasone, and omeprazole) originally intended for other indications with potential benefits for Alzheimer's patients.
Topics: Humans; Alzheimer Disease; Drug Repositioning; Propensity Score; Atorvastatin
PubMed: 38081829
DOI: 10.1038/s41467-023-43929-1