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Thyroid Research Jun 2023One of the common causes of suboptimal control of thyroid stimulating hormone (TSH) in levothyroxine-treated hypothyroidism is coadministration of proton pump inhibitors...
Effect of morning versus night-time administration of proton pump inhibitor (pantoprazole) on thyroid function test in levothyroxine-treated primary hypothyroidism: a prospective cross-over study.
BACKGROUND
One of the common causes of suboptimal control of thyroid stimulating hormone (TSH) in levothyroxine-treated hypothyroidism is coadministration of proton pump inhibitors (PPIs). Morning administration of pantoprazole has been shown to suppress intragastric pH to a greater extent. We therefore aimed to determine the effect of pantoprazole at different time points of the day on thyroid function test (TFT) in levothyroxine-treated overt primary hypothyroidism.
METHODS
In this single centre, hospital based, prospective, two arm cross-over study (AB, BA), participants were randomized into 2 groups based on morning (6:00 am - 7:00 am simultaneously with the scheduled levothyroxine tablet) (group M) and evening (30 min before dinner) intake of 40 mg pantoprazole tablet (group N). After the initial 6 weeks (period 1), a washout period of 1 week for pantoprazole was given, and then both the groups crossed over for another 6 weeks (period 2). Patients were instructed to continue the same brand of levothyroxine tablet at empty stomach 1-hour before breakfast. Serum TSH was measured at baseline, week 6, and week 13.
RESULTS
Data from 30 patients, who completed the study with 100% compliance, were analysed. Mean TSH values of the study participants were significantly higher both at week 6 and week 13 compared to the baseline. Mean baseline serum TSH concentrations for groups M and N were 2.70 (± 1.36), and 2.20 (± 1.06) µlU/mL, respectively. Mean serum TSH concentrations at the end periods 1 and 2 for group M were 3.78 (± 4.29), and 3.76 (± 2.77) while the levels in group N were 3.30 (± 1.90), and 4.53 (± 4.590) µlU/mL, respectively. There was a significant rise in serum TSH concentration across periods 1 and 2 in both the groups (F = 3.87, p = 0.03). Within group changes in TSH across periods 1 and 2 were not statistically significant. Similarly difference in TSH between the groups, either at 6 weeks or at 13 weeks, were also not statistically significant.
CONCLUSIONS
Concomitant use of pantoprazole, even for 6 weeks, leads to significant elevation in serum TSH in levothyroxine-treated patients who are biochemically euthyroid, irrespective of timing of pantoprazole intake. Early morning and night-time administration of pantoprazole have similar effect on TFT in these patients.
PubMed: 37259094
DOI: 10.1186/s13044-023-00156-6 -
Cureus Apr 2023Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis that affects many organ systems with varying disease severity. GPA commonly affects the sinuses and...
Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis that affects many organ systems with varying disease severity. GPA commonly affects the sinuses and lung parenchyma. However, GPA can affect the gastrointestinal tract and may present as colitis. Immunosuppressive therapy, like rituximab (RTX), is used for the management of this disease. Rituximab is generally well-tolerated but has rare side effects that have been shown to mimic colitis in inflammatory diseases. Our case is a 44-year-old female with a history of GPA who presented with dysphagia, abdominal pain, and diarrhea. The patient received a maintenance dose of RTX six months before the presentation. The patient was seronegative for anti-neutrophilic cytoplasmic antibodies against proteinase 3 (PR3 ANCA). Infectious etiology was ruled out. Esophagogastroduodenoscopy (EGD) and colonoscopy showed esophageal bleeding ulcers and diffuse colonic inflammation, respectively. Pathology was consistent with esophagitis and colitis. Colonic mucosal biopsy failed to show evidence of vasculitis. The patient was treated with sucralfate and intravenous pantoprazole with an improvement in the symptoms. The repeat endoscopy on an outpatient basis showed the patient had full mucosal healing, including histological healing. Our patient likely had rituximab-induced colitis and esophagitis.
PubMed: 37252552
DOI: 10.7759/cureus.38207 -
Revista Espanola de Enfermedades... Jun 2023A 68-year-old woman with stage IV pancreatic adenocarcinoma (liver and lymph node metastases) on first-line treatment with gemcitabine. As a non-oncological comorbidity,...
A 68-year-old woman with stage IV pancreatic adenocarcinoma (liver and lymph node metastases) on first-line treatment with gemcitabine. As a non-oncological comorbidity, the patient was anticoagulated with enoxaparin 8000 IU/24 hours because she had a mitral valve prosthesis. The patient made a medical consultation for presenting vomits which looked like coffee grounds and melaena. In the complete blood count, a hemoglobin of 7.5 g/dL was detected. Transfusion support, pantoprazole infusion (80 mg in 500 cc of 0.9% SSF every 12 hours) and parenteral nutrition were prescribed. Tranexamic was not prescribed due to the patient's cardiological history.
Topics: Female; Humans; Aged; Pancreatic Neoplasms; Adenocarcinoma; Duodenum; Hemorrhage
PubMed: 37232169
DOI: 10.17235/reed.2023.9738/2023 -
Experimental and Therapeutic Medicine Jun 2023The present network meta-analysis aimed to enhance the corresponding evidence with respect to the efficacy and safety of pharmaceuticals treatments. Frequentist network...
The present network meta-analysis aimed to enhance the corresponding evidence with respect to the efficacy and safety of pharmaceuticals treatments. Frequentist network meta-analysis was used. Medical literature up to November 2022 was searched for randomized clinical trials assessing the efficacy and safety of these pharmaceuticals, either compared with each other or compared with placebo. With the exception of ranitidine (300 mg four times daily) and vonoprazan (20 mg once daily) having lower safety than placebo, the efficacy and safety of the remaining treatments were superior to placebo. Cimetidine (400 mg four times daily) and pantoprazole (40 mg once daily) were ranked first in terms of efficacy. The frequentist network meta-analysis shows that for cimetidine (except 400 mg once daily), famotidine, rabeprazole, ilaprazole, lansoprazole (except 7.5 mg once daily) and omeprazole (except 10 mg once daily or 30 mg once daily), the efficacy comparison between the different doses of each of the aforementioned pharmaceuticals did not indicate statistically significant differences. In conclusion, pantoprazole (40 mg once daily) was the best choice for the initial non-eradication treatment of patients with duodenal ulcer, and cimetidine (400 mg twice daily), omeprazole (20 mg once daily), lansoprazole (15 mg once daily), ilaprazole (5 mg once daily) and rabeprazole (10 mg once daily) could be used as the first choice. If the aforementioned pharmaceuticals cannot be prescribed, famotidine (40 mg twice daily) is recommended.
PubMed: 37206569
DOI: 10.3892/etm.2023.11971 -
Biomedicines Apr 2023Glioblastoma (GBM) is the most prevalent and aggressive adult brain tumor. Despite multi-modal therapies, GBM recurs, and patients have poor survival (~14 months)....
Glioblastoma (GBM) is the most prevalent and aggressive adult brain tumor. Despite multi-modal therapies, GBM recurs, and patients have poor survival (~14 months). Resistance to therapy may originate from a subpopulation of tumor cells identified as glioma-stem cells (GSC), and new treatments are urgently needed to target these. The biology underpinning GBM recurrence was investigated using whole transcriptome profiling of patient-matched initial and recurrent GBM (recGBM). Differential expression analysis identified 147 significant probes. In total, 24 genes were validated using expression data from four public cohorts and the literature. Functional analyses revealed that transcriptional changes to recGBM were dominated by angiogenesis and immune-related processes. The role of MHC class II proteins in antigen presentation and the differentiation, proliferation, and infiltration of immune cells was enriched. These results suggest recGBM would benefit from immunotherapies. The altered gene signature was further analyzed in a connectivity mapping analysis with QUADrATiC software to identify FDA-approved repurposing drugs. Top-ranking target compounds that may be effective against GSC and GBM recurrence were rosiglitazone, nizatidine, pantoprazole, and tolmetin. Our translational bioinformatics pipeline provides an approach to identify target compounds for repurposing that may add clinical benefit in addition to standard therapies against resistant cancers such as GBM.
PubMed: 37189838
DOI: 10.3390/biomedicines11041219 -
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 -
Scientific Reports May 2023Breast cancer and diabetes are significant health challenges, and effective treatments for both diseases are lacking. Proton pump inhibitors (PPIs) have demonstrated...
Breast cancer and diabetes are significant health challenges, and effective treatments for both diseases are lacking. Proton pump inhibitors (PPIs) have demonstrated anticancer and hypoglycemic effects, but their mechanisms of action are not yet fully understood. We used the GeneCards and PharmMapper databases to identify therapeutic targets for diabetes, breast cancer and PPIs. We identified common targets and constructed a regulatory network of diseases and drugs using the STRING database and Cytoscape software. We also explored the binding between small molecule ligands and protein receptors using Discovery Studio software. We identified 33 shared targets for breast cancer, diabetes, and PPIs including lansoprazole, omeprazole, and pantoprazole, which play a critical role in fatty acid transport, insulin resistance, apoptosis, and cancer-related signaling pathways. Our findings demonstrated that PPIs had a strong affinity for AKT1 and MMP9. This study provides insights into the mechanisms of action of PPIs in breast cancer and diabetes and identifies AKT1 and MMP9 as critical targets for future drug development. Our findings highlight the potential of PPIs as a novel therapeutic approach for these challenging diseases.
Topics: Humans; Female; Proton Pump Inhibitors; Matrix Metalloproteinase 9; Anti-Ulcer Agents; Breast Neoplasms; Network Pharmacology; Diabetes Mellitus; 2-Pyridinylmethylsulfinylbenzimidazoles
PubMed: 37165049
DOI: 10.1038/s41598-023-34524-x -
The Turkish Journal of Gastroenterology... May 2023Gastroesophageal reflux disease is a common condition worldwide. There is no curative treatment for gastroesophageal reflux disease. Endoplasmic reticulum stress leads...
BACKGROUND
Gastroesophageal reflux disease is a common condition worldwide. There is no curative treatment for gastroesophageal reflux disease. Endoplasmic reticulum stress leads to the activation of the unfolded protein response and has an important role in inflammation. The aim is to determine the role of endoplasmic reticulum stress in the follow-up of individuals with gastroesophageal reflux disease and the temporal changes of endoplasmic reticulum stress markers with treatment.
METHODS
Twenty-four subjects in total were recruited prospectively, of whom 15 had nonerosive reflux disease. Two biopsies from 2 cm above the esophagogastric junction, 2 biopsies from gastric antrum mucosa, and 2 biopsies from gastric corpus mucosa were taken. Simultaneously, 2 tubes of venous blood samples were drawn from each individual (1 tube for studying the genetic markers and 1 tube for analyzing the CYP2C19 polymorphism).
RESULTS
The mean age was 42.3 ± 17.6 for women and 34.66 ± 11.2 for men. Pantoprazole, esomeprazole, rabeprazole, and lansoprazole preparations were used for treatment. There was no significant difference between tissue and blood samples for panel genes ATF-6, XBP-1, DDIT-3, DNAJC-10, and EIF-2-AK before treatment. There was a significant decrease in the level of ATF-6, XBP-1, DNAJC-9, EIF2-AK, and NF-2L-2 genes in blood after treatment. In the comparison of proton pump inhibitors, significant decreases in the expression of the ATF-6, XBP-1, and DNAJC-9 mRNAs were detected in blood from individuals after treatment.
CONCLUSION
Endoplasmic reticulum stress can be for evaluating the clinical improvement and the effectiveness of treatment in gastroesophageal reflux disease.
Topics: Male; Female; Humans; Young Adult; Adult; Middle Aged; Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Treatment Outcome; Proton Pump Inhibitors; Gastroesophageal Reflux; Lansoprazole; Rabeprazole; Endoplasmic Reticulum Stress
PubMed: 37158535
DOI: 10.5152/tjg.2023.21282 -
Journal of Clinical Medicine Apr 2023Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin...
BACKGROUND AND OBJECTIVES
Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin D insufficiency may occur in such patients.
MATERIALS AND METHODS
We recruited patients using a PPI (pantoprazole) for >12 months. The control group was represented by subjects attending the general practitioner not taking any PPI in the last 12 months. We excluded subjects using nutritional supplements or with diseases interfering with micronutrient blood levels. All subjects underwent blood sampling with full blood count, iron, ferritin, vitamin D, calcium, sodium, potassium, phosphate, zinc and folate.
RESULTS
We recruited 66 subjects: 30 in the PPI group and 36 in the control group. Long-term pantoprazole users had lower red blood cell count but similar hemoglobin. We did not find any significant difference in blood iron, ferritin, vitamin B12 and folate. Vitamin D deficit was observed more frequently in the PPI group (100%) than in controls (30%, < 0.001), with blood levels lower in pantoprazole consumers. No differences in calcium, sodium and magnesium were observed. Pantoprazole users had lower phosphate levels than controls. Finally, a non-significant trend for zinc deficiency was found in PPI users.
CONCLUSIONS
Our study confirms that chronic PPI users may encounter alterations in some micronutrients involved in bone mineral homeostasis. The effect on zinc levels deserves further investigation.
PubMed: 37109245
DOI: 10.3390/jcm12082910 -
Cureus Mar 2023Introduction The global proton pump inhibitors (PPIs) market was valued at US$ 2.9 billion in 2020 and is expected to exhibit a compound aggregated growth rate of 4.30%...
Introduction The global proton pump inhibitors (PPIs) market was valued at US$ 2.9 billion in 2020 and is expected to exhibit a compound aggregated growth rate of 4.30% during the forecast period (2020-2027), as they are regularly prescribed for many gastrointestinal disorders, and the treatment usually lasts for a longer period. PPIs are usually combined with antiemetics and prokinetic drugs. The price of PPIs for the same combination varies a lot, which can lead to a lot of financial burden on the patients. Objective To evaluate the cost ratio and percentage cost variation of commonly used PPIs in various combinations. Methodology The cost of different brands of commonly used PPIs in combination with other drugs was analyzed in our study. A total of 21 different combinations (10 capsules/tablets for oral use) were tabulated by referring to the "Monthly Index of Medical Specialities" October-December 2021, and 1mg online pharmacy. The cost ratio and percentage cost variation for various brands of a particular strength and dosage form were calculated and compared. Cost ratio > 2 and cost variation > 100% were considered significant. Results The results show a huge variation (1788.88%) in costs of different brands with the highest being rabeprazole 20 mg and domperidone 10 mg (cost ratio: 18.88, percentage cost variation: 1788.88%) in oral formulation, followed by pantoprazole 40 mg and itopride 150 mg. The minimum cost ratio (1.35) and percentage cost variation (1.35%) is for pantoprazole 40 mg and levosulpiride 75 mg. Logistic regression analysis between the number of brands and percentage cost variation gives an R value of 0.0923. Conclusion There is a wide variation in the prices of PPIs available in the market, which can inadvertently increase the financial burden of therapy on patients. Physicians need to be made aware of these price differences so that they can choose the best available alternative for patients, which can help in increasing compliance with the prescribed drugs.
PubMed: 37065352
DOI: 10.7759/cureus.36112