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European Journal of Pharmaceutical... Mar 2024As a widely used antidepressant that works by inhibiting the reuptake of serotonin, sertraline exerts an antidepressant effect depending on its concentration in the...
As a widely used antidepressant that works by inhibiting the reuptake of serotonin, sertraline exerts an antidepressant effect depending on its concentration in the brain, which might be limited by the blood-brain barrier (BBB). It is highly possible to combine proton pump inhibitors (PPIs) with sertraline in clinical trials. Nevertheless, the role played by PPIs in regulating the transport of sertraline across the BBB remains unclear. Here, the impact of PPIs on the distribution of sertraline in the brain and the mechanisms involved were investigated. A mouse brain distribution study showed that Omeprazole (OME), Pantoprazole (PAN), Ilaprazole (ILA), and Esomeprazole (ESO) increased the area under the brain concentration-time curves (AUC) for sertraline by 2.02-, 3.18-, 3.04-, and 4.21-fold, respectively, after the 14-day administration of PPIs. Besides, PPIs significantly increased the permeability of sertraline in brain perfusion experiments, with PAN having the highest rank order, followed by ILA, OME, and ESO. In the tail suspension test (TST), co-administration PPI groups showed significantly shorter immobility time than the control group. In vitro, four PPIs inhibited sertraline efflux in breast cancer resistance protein (BCRP)-overexpressing MDCKII cells, and showed a mixed inhibition type. In this study, PPIs were further found to inhibit the mRNA and protein expression of brain BCRP. To sum up, the findings of this study revealed that PPIs could enhance the brain distribution and antidepressant effect of sertraline, which may be attributed to the inhibition of BCRP expression at the BBB by PPIs.
Topics: Animals; Mice; Proton Pump Inhibitors; ATP Binding Cassette Transporter, Subfamily G, Member 2; Sertraline; Blood-Brain Barrier; Neoplasm Proteins; Omeprazole; Esomeprazole; Antidepressive Agents; Pantoprazole; 2-Pyridinylmethylsulfinylbenzimidazoles
PubMed: 38006986
DOI: 10.1016/j.ejps.2023.106653 -
BMJ Open Nov 2023The e-aluating the nhibition of tress rosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically...
INTRODUCTION
The e-aluating the nhibition of tress rosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE.
METHODS AND ANALYSIS
REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia, infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.
ETHICS AND DISSEMINATION
All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to - Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide.
TRIAL REGISTRATION NUMBER
NCT03374800.
Topics: Adolescent; Adult; Humans; Gastrointestinal Hemorrhage; Intensive Care Units; Pantoprazole; Pneumonia, Ventilator-Associated; Proton Pump Inhibitors; Respiration, Artificial; Randomized Controlled Trials as Topic
PubMed: 37968012
DOI: 10.1136/bmjopen-2023-075588 -
Journal of Feline Medicine and Surgery Oct 2023The primary objective of this study was to evaluate the prescription patterns and appropriateness of the use of gastroprotectant medication in cats.
OBJECTIVES
The primary objective of this study was to evaluate the prescription patterns and appropriateness of the use of gastroprotectant medication in cats.
METHODS
Pharmacy dispensation logs from an academic tertiary referral center were reviewed between 1 January 2018 and 31 December 2018. Cats that were administered proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, misoprostol, antacids or a combination were included. Data regarding medication, dosage, formulation, duration of administration, completeness of discharge instructions and clinical rationales for administration were obtained from medical records. The appropriateness of gastroprotectant use was assessed according to the American College of Veterinary Internal Medicine consensus statement guidelines.
RESULTS
Of the 110 cases, 67 (60.9%) were prescribed a gastroprotectant medication without an appropriate indication. The most common reason for prescription was acute kidney injury in 26/67 (38.8%). PPIs were the most common gastroprotectant medication administered in 95/110 (86.3%) cats, followed by sucralfate in 18/110 (16.4%) and H2RAs in 11/110 (10%). Of the 35 cases in which gastroprotectant therapy was indicated, the medication chosen or dosage administered was considered suboptimal in 16 (45.7%). Instructions regarding the duration of administration, potential adverse effects and timing of administration in relation to meals or other medications were inconsistently provided in discharge instructions to pet owners. Of the 29 cases discharged with omeprazole, only 13 (44.8%) instructions included a duration of administration, while 6 (20.7%) recommended continuing gastroprotectants indefinitely until further notice, 16 (55.2%) discussed the timing of the administration in relation to a meal and six (20.7%) mentioned potential adverse effects; none advised tapering of omeprazole before discontinuation.
CONCLUSIONS AND RELEVANCE
When prescribed, gastroprotectant medications were frequently prescribed injudiciously to cats in this referral population over a 12-month period. Discharge instructions to pet owners also often lacked information and recommendations regarding optimal administration, potential adverse effects, and tapering or discontinuation of the medications.
Topics: Humans; Cats; United States; Animals; Sucralfate; Tertiary Care Centers; Proton Pump Inhibitors; Omeprazole; Histamine H2 Antagonists
PubMed: 37874311
DOI: 10.1177/1098612X231201769 -
Advances in Therapy Dec 2023Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective,... (Observational Study)
Observational Study
INTRODUCTION
Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective, observational cohort study was to describe the characteristics and healthcare burden of patients with EE.
METHODS
We identified adults in the USA with an EE diagnosis between January 1, 2016 and February 28, 2019 in a linked dataset containing electronic health records (EHR) from the Veradigm Network EHR and claims data from Komodo Health. Patients were required to have 1 year of baseline data and 3 years of follow-up data. Patients were stratified by the number of PPI lines of therapy (LOT) during the 4-year study period. We descriptively captured patient characteristics and treatment patterns, along with all-cause and EE-related healthcare utilization and costs.
RESULTS
Among the 158,347 qualifying adults with EE, 71,958 (45.4%) had 1 PPI LOT, 14,985 (9.5%) had 2 LOTs, 15,129 (9.6%) had 3+ LOTs, and 56,275 (35.5%) did not fill a PPI prescription. Omeprazole and pantoprazole comprised more than 70% of any LOT, with patients commonly switching between the two. Mean (standard deviation) annualized all-cause and EE-related healthcare costs in the follow-up period were $16,853 ($70,507) and $523 ($3659), respectively. Both all-cause and EE-related healthcare costs increased with LOTs.
CONCLUSIONS
Patients with EE are commonly treated with prescription PPIs; however, 19.0% of patients cycled through multiple PPIs. Higher PPI use was associated with a higher comorbidity burden and higher healthcare costs compared to 0 PPI use.
Topics: Adult; Humans; United States; Electronic Health Records; Retrospective Studies; Insurance Claim Review; Proton Pump Inhibitors; Esophagitis
PubMed: 37837526
DOI: 10.1007/s12325-023-02688-7 -
Investigating Skin Rashes Associated With Pantoprazole Medication: Causes and Clinical Implications.Cureus Sep 2023Pantoprazole is a proton-pump inhibitor mainly used in treating various gastroesophageal disorders and frequently as prophylaxis for stress ulcers and gastrointestinal...
Pantoprazole is a proton-pump inhibitor mainly used in treating various gastroesophageal disorders and frequently as prophylaxis for stress ulcers and gastrointestinal bleeding in most patients admitted for in-hospital management. Hypersensitivity reactions to this medication have been reported, although the exact incidence and prevalence are unknown. Further studies on proton-pump inhibitor allergic reactions should be conducted to enable physicians to safely select and prescribe an alternative type of medication within the same drug class, confidently avoiding the allergenic molecular compound that the patient reacted to previously. We present a case of a 35-year-old male postoperative bariatric patient with no significant allergy history who developed an allergic skin rash a week after being discharged on pantoprazole 40 mg. His rash was itchy and distributed mainly over the torso and lower limbs, without any additional respiratory or gastrointestinal symptoms.
PubMed: 37799233
DOI: 10.7759/cureus.44623 -
Arquivos de Gastroenterologia 2023•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse...
•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse effects were fewer and milder in the gemifloxacin group. •Since treatment period was shorter and pills to be taken were fewer compared to quadruple treatment, patient compliance was significantly higher in the gemifloxacin group. Background - After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective - To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods - This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results - Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion - Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.
Topics: Humans; Gemifloxacin; Helicobacter pylori; Bismuth; Pantoprazole; Retrospective Studies; Drug Therapy, Combination; Helicobacter Infections; Amoxicillin; Metronidazole; Treatment Outcome; Gastritis; Anti-Bacterial Agents; Proton Pump Inhibitors
PubMed: 37792765
DOI: 10.1590/S0004-2803.230302-23-51 -
Cureus Sep 2023Vancomycin is one of the most empirically used antibiotics in severely ill patients in hospitalized settings. Vancomycin-induced thrombocytopenia (VITP) is a rare and...
Vancomycin is one of the most empirically used antibiotics in severely ill patients in hospitalized settings. Vancomycin-induced thrombocytopenia (VITP) is a rare and potentially life-threatening complication that requires immediate recognition. Platelet destruction is largely immune-mediated and results in a precipitous drop in the platelet count over a short period of time. Most cases of VITP are drug-dependent, as discontinuation of the offending agent frequently results in a timely return to baseline to pre-exposure platelet levels. Here, we present a case of severe vancomycin-induced thrombocytopenia in a 35-year-old female with a history of multiple comorbidities who presented with pneumonia. She was undergoing treatment with vancomycin and piperacillin-tazobactam and developed thrombocytopenia within 24 hours of hospitalization. The patient was on a loading dose of 1250 mg intravenous vancomycin every 24 hours and piperacillin-tazobactam 3.375 g intravenously every six hours for presumed community-acquired pneumonia. Her other medications included ondansetron, bupropion, sertraline, tamsulosin, pantoprazole, ergocalciferol, and insulin glargine. Additionally, the patient was placed on a prophylactic dose of enoxaparin while in-patient. The patient's thrombocytopenia resolved with discontinuation of vancomycin. Clinicians should be well-informed about which medications can trigger thrombocytopenia whenever starting a medication in such cases.
PubMed: 37753064
DOI: 10.7759/cureus.45945 -
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 -
Geriatrics (Basel, Switzerland) Aug 2023Pharmacogenomic factors affect the susceptibility to drug-drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of...
Identification of Drugs Acting as Perpetrators in Common Drug Interactions in a Cohort of Geriatric Patients from Southern Italy and Analysis of the Gene Polymorphisms That Affect Their Interacting Potential.
BACKGROUND
Pharmacogenomic factors affect the susceptibility to drug-drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of 290 older adults and analysed the prevalence of gene polymorphisms that can increase their interacting potential. We also pinpointed clinical decision support systems (CDSSs) that incorporate pharmacogenomic factors in DDI risk evaluation.
METHODS
Perpetrator drugs were identified using the Drug Interactions Flockhart Table, the DRUGBANK website, and the Mayo Clinic Pharmacogenomics Association Table. Allelic variants affecting their activity were identified with the PharmVar, PharmGKB, dbSNP, ensembl and 1000 genome databases.
RESULTS
Amiodarone, amlodipine, atorvastatin, digoxin, esomperazole, omeprazole, pantoprazole, simvastatin and rosuvastatin were perpetrator drugs prescribed to >5% of our patients. Few allelic variants affecting their perpetrator activity showed a prevalence >2% in the European population: CYP3A4/5*22, *1G, *3, CYP2C9*2 and *3, CYP2C19*17 and *2, CYP2D6*4, *41, *5, *10 and *9 and SLC1B1*15 and *5. Few commercial CDSS include pharmacogenomic factors in DDI-risk evaluation and none of them was designed for use in older adults.
CONCLUSIONS
We provided a list of the allelic variants influencing the activity of drug perpetrators in older adults which should be included in pharmacogenomics-oriented CDSSs to be used in geriatric medicine.
PubMed: 37736884
DOI: 10.3390/geriatrics8050084 -
BioMed Research International 2023Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the...
BACKGROUND
Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion.
METHODS
Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation.
RESULTS
The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups.
CONCLUSION
Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.
Topics: Male; Animals; Rats; Pantoprazole; Gastrins; Alkaline Phosphatase; Octreotide; Bone Diseases, Metabolic; Parathyroid Hormone
PubMed: 37711876
DOI: 10.1155/2023/2594664