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Cureus Jul 2023Objectives This prospective study assessed the effectiveness and patient satisfaction of four-week omeprazole therapy in acid peptic disease (APD). Methods This was an...
Objectives This prospective study assessed the effectiveness and patient satisfaction of four-week omeprazole therapy in acid peptic disease (APD). Methods This was an observational, post-marketing, real-world evidence, patient-reported outcome (PRO) measures study. Patients visiting the five study sites across India with symptoms of APD, and who were prescribed oral omeprazole (20/40 mg per day) for at least four weeks were enrolled after obtaining informed consent. Study assessments included frequency and severity of symptoms and overall satisfaction reported by the patients using the Patient Assessment of Gastrointestinal Disorder Symptom Severity Index (PAGI-SYM) questionnaire. The satisfaction with therapy was reported by the patients using the Treatment Satisfaction Questionnaire for Medication (TSQM) questionnaire. Both PAGI-SYM and TSQM were reported by patients on days 14 and 28. Omeprazole safety was assessed based on the adverse events reported by the patients. Results A total of 96 (62 males and 34 females) patients were included in the study, of which 38.54% had significant findings related to APD at baseline. The proportion of patients with symptoms reduced to 16.67% on day 14 and 8.33% on day 28 with omeprazole therapy. The PAGI-SYM total scores at baseline were 41.32 (15.487), which reduced to 20.86 (11.620) on day 14 (p < 0.0001), and to 8.93 (8.361) on day 28 (p < 0.0001). Significant reductions were also seen in individual symptom scores. The TSQM total scores increased to 36.67 (range: 13 to 63) on day 28 from 34.69 (range: 12 to 58) on day 14. Improvement in scores for all domains of TSQM (effectiveness, convenience, and global satisfaction) was seen on day 28. Improvement in reflux symptoms was reported by 46.74% and 68.48% of patients on day 14 and day 28, respectively. Four (4.17%) patients reported adverse events, which were of mild severity and were unrelated to omeprazole. Conclusions Omeprazole provides significant improvement in PAGI-SYM and TSQM questionnaires on day 14 and day 28. Patients reported the omeprazole-based therapy as effective, convenient, and satisfactory. Omeprazole therapy is safe and effective for the treatment of APD and shows good improvement in APD in patients suffering from duodenal ulcers, gastric ulcers, and reflux oesophagitis.
PubMed: 37593315
DOI: 10.7759/cureus.41994 -
Journal of Veterinary Internal Medicine 2023Rebound gastric hyperacidity (RGH) secondary to hypergastrinemia has been suggested to contribute to the rapid recurrence of equine squamous gastric disease (ESGD) in...
Evaluation of the effects of medium-term (57-day) omeprazole administration and of omeprazole discontinuation on serum gastrin and serum chromogranin A concentrations in the horse.
BACKGROUND
Rebound gastric hyperacidity (RGH) secondary to hypergastrinemia has been suggested to contribute to the rapid recurrence of equine squamous gastric disease (ESGD) in horses after discontinuation of omeprazole.
HYPOTHESIS/OBJECTIVES
To evaluate changes in serum gastrin and chromogranin A (CgA) concentrations in response to medium-term (57-day) omeprazole treatment and after omeprazole discontinuation.
ANIMALS
Fourteen mature Thoroughbred racehorses in simulated race training.
METHODS
Horses received 2.28 g of oral omeprazole PO q24h for 57 days within a 61-day period, excluding a withholding period applied mid-protocol during which treatment was stopped as part of a concurrent study. Serum samples were collected on day 0 before omeprazole treatment, on day 1 of each week of the treatment period, and for an additional 5 weeks after discontinuation of treatment. Serum gastrin and CgA concentrations were analyzed using radioimmunoassay (RIA) and ELISA, respectively.
RESULTS
Median serum gastrin concentrations increased 2.5-fold from baseline to day 7 (P < .001) but did not increase further during the omeprazole treatment period. Median serum gastrin concentrations returned to baseline within 2 to 4 days after administration of the last dose of omeprazole. No effect of treatment or discontinuation was seen in serum CgA concentrations.
CONCLUSIONS AND CLINICAL IMPORTANCE
Serum gastrin concentrations increased in response to omeprazole treatment but returned to baseline within 2 to 4 days after the last dose of omeprazole. No effect of treatment or discontinuation was seen in serum CgA concentrations. Our results do not support the use of tapering protocols in horses.
Topics: Horses; Animals; Omeprazole; Chromogranin A; Anti-Ulcer Agents; Gastrins; Stomach
PubMed: 37390114
DOI: 10.1111/jvim.16795 -
Antimicrobial Agents and Chemotherapy Oct 2023Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug...
Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1-15), followed by RIF40 (days 16-30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%-115%); tolbutamide, 80% (74%-86%); omeprazole, 55% (47%-65%); dextromethorphan, 77% (68%-86%); midazolam, 62% (49%-78%), and 117% (105%-130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number NCT04525235.
Topics: Adult; Humans; Cytochrome P-450 CYP1A2; Midazolam; Cytochrome P-450 CYP2D6; Caffeine; Rifampin; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Dextromethorphan; Tolbutamide; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Omeprazole; Drug Interactions; Tuberculosis, Pulmonary; Digoxin
PubMed: 37768317
DOI: 10.1128/aac.00683-23 -
Cancers Nov 2023The concept of exposome refers to the total of harmful and beneficial environmental exposures that can help predict the organism's biological responses over time....
INTRODUCTION
The concept of exposome refers to the total of harmful and beneficial environmental exposures that can help predict the organism's biological responses over time. Ultraviolet radiation (UVR) from sun exposure has been recognized as the main etiological agent of skin cancer, and squamous cell carcinoma (SCC) is one most commonly associated with chronic exposure. However, in recent years, evidence suggests that lifestyle, environmental pollution, and contaminants in water and food can have an influence.
OBJECTIVES
To study the relationship between SCC and sun exposure, pollution, stress, and lifestyle in a Spanish cohort.
MATERIALS AND METHOD
A multicenter case-control study was carried out in which 13 dermatologists from different regions of Spain recruited cases and controls between April 2020 and August 2022. The group of cases were patients diagnosed with SCC and, as a control group, people who attended Dermatology consultations as companions with no history of skin cancer.
RESULTS
A total of 62 patients with SCC and 126 controls were included (62.9% males, median age 76.46 (10.1) and 33.3%, median age 55.7 (15), respectively). The SCC group had experienced more outside work than the controls (75% vs. 22.4%, < 0.001), less recreational exposure (sunbathing, = 0.05, and outdoor sports, = 0.01), and a lower annual income ( = 0.01), with an increase in tobacco exposure ( < 0.001), without differences in other carcinogens, such as ionizing radiation or chemical exposure. The control group had a higher daily screentime use ( < 0.001) and practiced more relaxation activities ( = 0.03). A higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with SCC ( < 0.05). Some chronic medications (anxiolytics, antidepressants, beta-blockers, statins, hydrochlorothiazide, ACE inhibitors, metformin, and omeprazole) were also statistically associated with SCC. Statistical significance for all aforementioned variables was maintained in the multivariate analysis ( < 0.05).
CONCLUSIONS
The study found a significant association between SCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers promoting sun-safe behaviors and stress-reducing activities, in addition to adequate skin photoprotection in patients under certain medications associated with SCC.
PubMed: 38001636
DOI: 10.3390/cancers15225376 -
Frontiers in Pharmacology 2023Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine,...
Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine, which may lead to elevated serum levels of the drug. However, the existing literature on this topic is limited. Therefore, we conducted a study using VigiBase to investigate the potential over-reporting of infections associated with clozapine, to explore the presence of dose-dependency, and to investigate the underlying mechanism. Disproportionality analyses were performed using VigiBase to assess the association between clozapine and all types of infections, the association between clozapine-associated infections and neutropenia, the association between clozapine-associated infections and agranulocytosis, the dose-effect relationship between clozapine and infections, and the interaction between clozapine and the main strong CYP450 inhibitors using reports carried out until 11 April 2023. A statistically significant signal of infections was observed with clozapine, as indicated by an information component of 0.43 [95% CI: (0.41-0.45)]. The most commonly reported infections were respiratory and gastrointestinal in nature. Neutropenia showed weaker association with clozapine-associated reports of infections compared to other clozapine-associated reports [X2 (1, N = 204,073) = 454; < 0.005], while agranulocytosis demonstrated a stronger association with clozapine-associated reports of infections [X2 (1, N = 204,073) = 56; < 0.005]. No evidence of dose-dependency was observed. Among the 17 tested CYP inhibitors, significant drug-drug interactions were found with clarithromycin, metronidazole, valproic acid, lansoprazole, omeprazole, amiodarone, and esomeprazole. Our study revealed a significant safety signal between clozapine use and infections, predominantly respiratory and gastrointestinal infections. The co-administration of clozapine with valproic acid or proton pump inhibitors may potentially contribute to an increased risk of infection. Further vigilance is warranted in clinical practice, and consideration of therapeutic drug monitoring of clozapine in cases involving concomitant use of these drugs or in the presence of infections may be beneficial.
PubMed: 37849735
DOI: 10.3389/fphar.2023.1260915 -
Clinical Pharmacokinetics Jul 2023Posaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV)...
BACKGROUND AND OBJECTIVE
Posaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV) solution, oral suspension (OS) and delayed-release tablets (DRTs), OS is the preferred formulation for pediatric use because of potential safety concerns associated with an excipient in the IV formulation and difficulty in swallowing intact tablets by children. However, poor biopharmaceutical characteristics of the OS formulation leads to an unpredictable dose-exposure profile of PSZ in children, potentially risking therapeutic failure. The goal of this study was to characterize the population pharmacokinetics (PK) of PSZ in immunocompromised children and assess therapeutic target attainment.
METHODS
Serum concentrations of PSZ were collected retrospectively from records of hospitalized patients. A population PK analysis was performed in a nonlinear mixed-effects modeling framework with NONMEM (v7.4). The PK parameters were scaled to body weight, then potential covariate effects were assessed. The final PK model was used to evaluate recommended dosing schemes through simulation of target attainment (as a percentage of the population having steady-state trough concentrations above the recommended target) using Simulx (v2021R1).
RESULTS
Repeated measurement data of 202 serum concentrations of total PSZ were acquired from 47 immunocompromised patients between 1 and 21 years of age receiving PSZ either intravenously or orally, or both. A one-compartment PK model with first-order absorption and linear elimination best fit the data. The estimated absolute bioavailability (95% confidence interval) for suspension (F) was 16% (8-27%), which was significantly lower than the reported tablet bioavailability (F) [67%]. F was reduced by 62% and 75% upon concomitant administration with pantoprazole (PAN) and omeprazole (OME), respectively. Famotidine resulted in a reduction of F by only 22%. Both fixed dosing and weight-based adaptive dosing provided adequate target attainment when PAN or OME were not coadministered with the suspension.
CONCLUSIONS
The results of this study revealed that both fixed and weight-based adaptive dosing schemes can be appropriate for target attainment across all PSZ formulations, including suspension. Additionally, covariate analysis suggests that concomitant proton pump inhibitors should be contraindicated during PSZ suspension dosing.
Topics: Adult; Humans; Child; Retrospective Studies; Administration, Oral; Invasive Fungal Infections; Antifungal Agents; Triazoles; Tablets; Suspensions
PubMed: 37179512
DOI: 10.1007/s40262-023-01254-2 -
Saudi Journal of Biological Sciences Aug 2023() has been reported to have a numeral of biological properties. Though, the influence of this plant extract on stomach ulceration is yet stated. Thirty rats...
() has been reported to have a numeral of biological properties. Though, the influence of this plant extract on stomach ulceration is yet stated. Thirty rats arbitrarily alienated 5 groups: the normal group, the ulcerated control group, the omeprazole group, and 2 investigational groups. Normal and ulcerated control groups were gavage by mouth 10% Tween 20. Omeprazole group fed orally 20 mg/kg omeprazole. Investigational group's gavage of 250 mg/kg and 500 mg/kg ethanol extracted 10% Tween 20, correspondingly. Later another hour, the normal group gavage 10% Tween 20, and groups 2-5 gavage absolute ethanol. Afterward additional hours altogether rats were sacrificed. The ulcerated control group displayed extensive apparent stomach epithelial damage escorted by reduced stomachs mucus excretion and pH stomach contented. extract meaningfully condensed ethanol-induced gastric lacerations, for example, demonstrated via augmented gastric mucus and pH stomach contents, condensed ulceration expanse, decreased or lack of edema, and leucocyte penetration hypodermic coat. In stomach epithelial homogenate, extract revealed important upsurge superoxide dismutase (SOD), catalase (CAT) actions, expressively diminished malondialdehyde (MDA) level. Furthermore, extract augmented strength periodic acid-Schiff (PAS) stain stomach mucosa, besides formed up-regulation heat shock protein 70 (HSP 70) proteins down-regulation the Bcl-2-associated X protein (Bax) protein gastric mucosal. extract lessened the level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and improved the quantity of interleukin-10 (IL-10). Acute toxicity greater dosage of 500 mg/kg extract organized not obvious at all toxicology symbols might improve self-protective tools against stomach epithelial abrasions. extract presented gastroprotective effects that could be due to capability upsurge pH then mucus discharge, rise SOD and CAT, decrease MDA quantity, up-regulating HSP 70 proteins, down-regulating Bax protein, and moderate provocative cytokines.
PubMed: 37415859
DOI: 10.1016/j.sjbs.2023.103711 -
Contemporary Clinical Trials Oct 2023Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics....
BACKGROUND
Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock.
METHODS
This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality.
DISCUSSION
This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock.
TRIAL REGISTRATION
This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.
PubMed: 37625587
DOI: 10.1016/j.cct.2023.107319 -
Cureus Mar 2024As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and... (Review)
Review
As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and appropriate diagnosis, adequate care, and a multidisciplinary approach to the management of patients. This systematic review explores the role of proton pump inhibitors (PPIs) in IPF and answers the question, "Does proton pump inhibitor improve only the prognosis of gastroesophageal associated idiopathic pulmonary fibrosis or for other types of idiopathic pulmonary fibrosis too?" We used PubMed (PMC) and Google Scholar for data collection for this systematic review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting this review. After in-depth literature screening and quality appraisal, 12 articles were selected for this systematic review. On the one hand, the efficacy of PPI therapy is supported by research such as the CAPACITY and ASCEND trials, a pilot randomized control trial (RCT) investigating the role of omeprazole in IPF and a bidirectional two-sample Mendelian randomization (MR) study, respectively. On the other hand, a systematic review and meta-analysis on antacid and antireflux surgery in IPF negate these results and show no statistical significance. Questions regarding the efficacy of PPI therapy must be dealt with in an adequately powered multicenter and double-blinded randomized control trial. The anti-inflammatory properties of antacids can serve as the cornerstone for future trials. In the following systematic review, antacid, antireflux therapy, omeprazole, and proton pump therapy are synonymous with stomach acid suppression therapy.
PubMed: 38606271
DOI: 10.7759/cureus.55980 -
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