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PloS One 2024Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are...
Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.
Topics: Animals; Pantoprazole; Sheep; Female; Injections, Subcutaneous; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Abomasum; Administration, Intravenous; Cross-Over Studies; Injections, Intravenous
PubMed: 38865425
DOI: 10.1371/journal.pone.0304533 -
Medecine Tropicale Et Sante... Mar 2024Accidental ingestion of a foreign body into the gastrointestinal tract is not uncommon, however the development of hepatic abscesses secondary to digestive perforation...
Accidental ingestion of a foreign body into the gastrointestinal tract is not uncommon, however the development of hepatic abscesses secondary to digestive perforation by a foreign body is rare. We report the case of pyogenic hepatic abscesses secondary to gastric perforation by a fishbone complicated by acute peritonitis. A 53-year-old patient was admitted to our hospital with the main complaints: diffuse abdominal pain with vomiting in a context of fever and physical asthenia. A painful febrile hepatomegaly with jaundice was objectified, as well as a non-specific biological inflammatory syndrome. An initial abdominopelvic CT scan revealed multifocal liver abscesses. Faced with the initial therapeutic failure associating parenteral antibiotic therapy and abscess drainage, a second abdominal CT scan identified a foreign body straddling the antropyloric wall and segment I of the liver.A xypho-pelvic midline laparotomy was performed with nearly 200 cc of peritoneal fluid coming out. A fishbone approximately 5 cm long was extracted by laparotomy, followed by gastric closure with omentum, peritoneal cleansing and drainage. Symptomatic adjuvant treatment was initiated, including a proton pump inhibitor (Pantoprazole). He also benefited from transfusion support in the face of anemia. Antibiotic therapy was continued for a total of 2 weeks after surgery. The evolution was favorable with follow-up imaging at 3 months, showing complete resorption of the hepatic abscesses.
Topics: Humans; Middle Aged; Peritonitis; Male; Liver Abscess, Pyogenic; Foreign Bodies; Acute Disease; Senegal; Stomach
PubMed: 38846121
DOI: 10.48327/mtsi.v4i1.2024.390 -
CPT: Pharmacometrics & Systems... Jun 2024Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with...
Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the body size metric that best guides dosing, but pharmacokinetic (PK) trials using traditional techniques are limited by the need for larger sample sizes and frequent blood sampling. Physiologically-based PK (PBPK) models are an attractive alternative that can account for physiologic-, genetic-, and drug-specific changes without the need for extensive clinical trial data. In this study, we explored the effect of obesity on pantoprazole PK and evaluated label-suggested dosing in this population. An adult PBPK model for pantoprazole was developed using data from the literature and accounting for genetic variation in CYP2C19. The adult PBPK model was scaled to children without obesity using age-associated changes in anatomical and physiological parameters. Lastly, the pediatric PBPK model was expanded to children with obesity. Three pantoprazole dosing strategies were evaluated: 1 mg/kg total body weight, 1.2 mg/kg lean body weight, and US Food and Drug Administration-recommended weight-tiered dosing. Simulated concentration-time profiles from our model were compared with data from a prospective cohort study (PAN01; NCT02186652). Weight-tiered dosing resulted in the most (>90%) children with pantoprazole exposures in the reference range, regardless of obesity status or CYP2C19 phenotype, confirming results from previously published population PK models. PBPK models may allow for the efficient study of physiologic and developmental effects of obesity on PK in special populations where clinical trial data may be limited.
PubMed: 38837864
DOI: 10.1002/psp4.13167 -
Future Science OA 2024Ilaprazole due to its pharmacokinetic variability does not affect the clopidogrel efficacy during concomitant use. Prediction of DDI for Clopidogrel and PPIs performed...
Ilaprazole due to its pharmacokinetic variability does not affect the clopidogrel efficacy during concomitant use. Prediction of DDI for Clopidogrel and PPIs performed using (DDI-Pred) Way2Drug software. The probabilities ΔP, which estimate the potential DDIs resulting from interaction with CYP450 isoenzymes. Positive ΔP-values for CYP2C19 (0.955) indicate that it is involved in the drug interaction of Ilaprazole and Clopidogrel. Pantoprazole and Ilaprazole were found to have a low probability of CYP2C19 inhibition Compared with other PPIs, Pantoprazole and Ilaprazole were found to have a low probability of CYP2C19 inhibition; Since Ilaprazole has pharmacokinetic variability, further and studies are required on the ilaprazole and clopidogrel combination to assess the effect of drug-drug interaction.
PubMed: 38817377
DOI: 10.2144/fsoa-2023-0277 -
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 -
Pharmacological Research Jun 2024Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6... (Review)
Review
Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.
Topics: Humans; Low Density Lipoprotein Receptor-Related Protein-6; Neoplasms; Animals; Antineoplastic Agents; Molecular Targeted Therapy; Wnt Signaling Pathway
PubMed: 38710241
DOI: 10.1016/j.phrs.2024.107200 -
Frontiers in Endocrinology 2024The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea... (Clinical Trial)
Clinical Trial
The prophylactic antiemetic therapies in management of differentiated thyroid cancer patients with radioactive iodine therapy: a single-center, non-randomized clinical trial.
OBJECTIVE
The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy.
METHOD
We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases.
RESULTS
A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (<0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders.
CONCLUSIONS
In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight.
Topics: Humans; Male; Female; Middle Aged; Antiemetics; Adult; Iodine Radioisotopes; Aged; Vomiting; Nausea; Young Adult; Adolescent; Thyroid Neoplasms; Ondansetron; Quality of Life
PubMed: 38706697
DOI: 10.3389/fendo.2024.1310223 -
BMC Medical Research Methodology May 2024During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies.
OBJECTIVE
To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring.
METHODS
REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022.
RESULTS
The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted.
CONCLUSION
Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.
Topics: Humans; COVID-19; Pantoprazole; SARS-CoV-2; Intensive Care Units; Pandemics; Female; Respiration, Artificial; Male; Clinical Protocols; Middle Aged; Gastrointestinal Hemorrhage; Anti-Ulcer Agents
PubMed: 38704520
DOI: 10.1186/s12874-024-02233-2 -
Gut Microbes 2024Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by...
Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing (ESBL-). The combination of inulin and pantoprazole (IP) significantly reduced ESBL- fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with or also reduced ESBL- fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant . The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.
Topics: Animals; Inulin; Mice; Gastrointestinal Microbiome; Escherichia coli; Feces; Amoxicillin; Pantoprazole; Drug Resistance, Multiple, Bacterial; beta-Lactamases; Dysbiosis; Anti-Bacterial Agents; Escherichia coli Infections; Female; Prebiotics
PubMed: 38685762
DOI: 10.1080/19490976.2024.2347021 -
Antibiotics (Basel, Switzerland) Apr 2024Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for () eradication. We compared...
Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for () eradication. We compared CT and BQT as the first lines of treatment in a randomized controlled trial. Consecutive patients with H. pylori diagnosed by concordance of both a urea breath test and histology were recruited. For BQT, patients received 3 Pylera capsules q.i.d.; for CT, 1000 mg of amoxicillin b.i.d, 500 mg of clarithromycin b.i.d and 500 mg of metronidazole b.i.d. As a proton pump inhibitor, 40 mg of pantoprazole b.i.d was administered. Both regimens lasted 10 days. In total, 46 patients received CT and 38 BQT. Both groups were comparable for age ( = 0.27) and sex ( = 0.36). We did not record any drop outs; therefore, the intention to treat and per protocol rates coincided. The most common symptoms were heartburn and post-prandial fullness, which were equally present in both groups. The success rate was 95.6% for CT and 100% for BQT ( = 0.56). Side effects were recorded in 23.9% and 31.6% of patients in the CT and BQT arms, respectively ( = 0.47). The most common ones were abdominal pain (8) and diarrhea (6). In conclusion, CT and BQT are equally effective in our area with high clarithromycin resistance, southern Italy, and showed comparable safety.
PubMed: 38667024
DOI: 10.3390/antibiotics13040348