Proton Pump Inhibitors Pantoprazole Research Articles

Metabolites are overlooked in environmental risk assessments and monitoring of pharmaceuticals: The case study of pantoprazole

The proton-pump inhibitor pantoprazole (PPZ) is one of the most consumed pharmaceuticals worldwide. Despite its high usage, reported PPZ concentrations in environmental water samples are comparatively low, which can be explained by the extensive metabolism of PPZ in the human body. Since most previous studies did not consider human PPZ metabolites it can be assumed that the current environmental exposure associated with the application of PPZ is substantially underestimated. In our study, 4′-O-demethyl-PPZ sulfide (M1) was identified as the predominant PPZ metabolite by analyzing urine of a PPZ consumer as well as the influent and effluent of a wastewater treatment plant (WWTP) using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS). M1 was found to be ubiquitously present in WWTP effluents (max. concentration: 3 000 ng/L) and surface waters in Germany. On average, the surface water concentrations of M1 were approximately 30 times higher than those of the parent compound PPZ. Laboratory scale experiments demonstrated that activated carbon can considerably adsorb M1 und thus improve its removal during wastewater and drinking water treatment. Laboratory ozonation experiments showed a fast oxidation of M1, accompanied by the formation of several ozonation products. Certain ozonation products (identities confirmed via synthesized reference standards) were also detected in water samples collected after ozonation in a full-scale WWTP. Overall lower signal intensities were observed in the effluents of a sand filter and biologically active granular activated carbon filter, suggesting that the compounds were significantly removed during these post-ozonation treatment stages.

Abstract CT140: A phase 1 study of the IAP inhibitor xevinapant (Debio 1143) to evaluate food effect and drug-drug interactions with a proton pump inhibitor in healthy volunteers

Abstract INTRODUCTION: Xevinapant is an oral IAP (inhibitor of apoptosis protein) inhibitor designed to restore cancer cell sensitivity to apoptosis, thereby enhancing the efficacy of chemoradiotherapy (CRT) and radiotherapy (RT). Xevinapant 200 mg/d (d1-14, Q3W) + CRT showed clinical benefit vs placebo + CRT in a phase 2 study of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN; NCT02022098). Two phase 3 studies are currently ongoing evaluating xevinapant in combination with CRT (TrilynX; NCT04459715) or RT (XRay Vision; NCT05386550) in patients with LA SCCHN, with dosing under fasting conditions or without regard to food, respectively. METHODS: A 2-stage study (Debio 1143-107) was conducted to assess the effect of food on 2 different formulations of xevinapant and the effect of co-administration with the proton pump inhibitor pantoprazole to evaluate the effect of high gastric pH on bioavailability of xevinapant. Stage 1 was an open-label, randomized, 4-arm, crossover study with 26 healthy volunteers (HV) treated with a single oral dose of xevinapant 200 mg in fasted or fed (high-fat diet) conditions with 2 different formulations. Stage 2 was a randomized, 2-way crossover study with 12 HV treated with a single oral dose of xevinapant 200 mg with or without pantoprazole. Pharmacokinetics (PK) and pharmacodynamics (PD) samples (Ciap1 levels in peripheral blood mononuclear cells [PBMCs]) were collected over 72 h post dose. The utilization of HV to address clinical pharmacology aspects of xevinapant was justified by holistic assessment of the toxicology, safety, and pharmacology profiles. RESULTS: Following a single dose of xevinapant 200 mg, exposures in HV under fasted conditions were consistent with those observed previously in cancer patients. Xevinapant formulations were bioequivalent and were considered safe and well tolerated in both fasted and fed conditions. Food delayed Tmax and decreased xevinapant Cmax by 39% but did not meaningfully alter the extent of absorption of xevinapant, as evidenced by no change in AUC, which is the most relevant exposure metric for efficacy based on xevinapant’s mechanism of action. Stage 2 data indicated that the PK of xevinapant was not affected by treatment with pantoprazole. Ciap1 levels in PBMCs decreased at least 4-fold compared to the baseline for all treatments and were reduced up to 72 h post single dose. No relevant differences in PD were observed across treatments. PK simulations indicated no relevant change in AUC and no impact on target engagement at steady state with food. CONCLUSION: These data indicate that xevinapant can be administered without regard to food or gastric acid reducing agents, which would be advantageous for patient convenience and compliance. Citation Format: Valérie Nicolas-Métral, Elisabeth Rouits, Camille Riff, Dany Spaggiari, Norbert Wiedemann, Pierre Colin, Eleanor Harrison-Moench, Rafael Crabbé, Heidi Nauwelaerts, Andreas Schroeder, Carolina Haefliger, Yulia Vugmeyster. A phase 1 study of the IAP inhibitor xevinapant (Debio 1143) to evaluate food effect and drug-drug interactions with a proton pump inhibitor in healthy volunteers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT140.

Варианты патогенетического лечения аспирининдуцированных гастроэнтеропатий у лиц с хронической ишемической болезнью сердца

Aim: Evaluation of Rebamipide treatment efficiency for aspirin-induced gastroduodenopathy in the patients with stable coronary heart disease (CHD). Design: Randomised controlled study. Materials and methods: In the course of the conducted research 340 CHD patients receiving long-term acetylsalicylic acid therapy in cardioprotective doses were studied. All the patients received complete clinical laboratory examination. For CHD verification there was applied selective method of coronary angiography. Gastroduodenopathy was verified by esophagogastroduodenoscopy. In both cases frequency and structure of the aforesaid events were assessed. For aspirin-induced gastroduodenopathy treatment there were applied either endogenic prostaglandin stimulant Rebamipide in combination with proton pump inhibitor (PPI) Pantoprazole (study group, n = 26) or Pantoprazole only (control group, n = 25). Prior to initiating therapy and on completion all the patients were taken blood samples for evaluation of prostaglandin E2 (PGE2) and proinflammatory cytokines (interleukine-1β Il-1β and interleukine-6 Il-6, TNF-α) levels in blood serum for verification of pathogenetic mechanisms in erosive or ulcer-bearing areas developing in gastrointestinal mucosa in association with long-term aspirin therapy. Соntrol group consisted of 26 CHD patients with no evidence of gastroduodenopathy. Statistical processing of the received data was conducted with the software program “Statistics 10.0”. Results. Aspirin-induced gastroduodenopathy was identified in 51 out of 340 (15,0%) cases. According to esophagogastroduodenoscopy data, erosions of the body and antrum of stomach were prevailing (43,1%) over all the erosive damages. CHD patients before the gastroduodenopathy treatment had significantly lower PGE2 levels in comparison with control group (p < 0,01), while proinflammatory cytokines indices were higher (p < 0,001). On the treatment completion 19 patients in the control group did not show endoscopic evidence of gastroduodenopathy, the laboratory findings tended to normalization. Gastric mucosa condition in the study group stabilized in all the cases, which was confirmed by statistically significant PGE2 level positive alterations (p < 0,001) and also cytokine profile alterations (TNF-α: p < 0,001; Il-1β and Il-6: p < 0,01). Conclusion. The presented study demonstrates clinical features of aspirin-induced gastroduodenopathy development in the CHD patients and proposes possible ways of correction. Key words: aspirin-induced gastroduodenopathy, acetylsalicylic acid, prostaglandin E2, proinflammatory cytokines, rebamipide.

REVISE: re-evaluating the inhibition of stress erosions in the ICU—statistical analysis plan for a randomized trial

BackgroundThe REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients.ObjectiveTo outline the statistical analysis plan for the REVISE trial.MethodsREVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated.ResultsThe primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile 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 concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment.ConclusionsThis statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide.Trial registrationwww.ClinicalTrials.gov NCT03374800. November 21, 2017.

Study of the empirical role of proton pump inhibitor therapy on laryngopharyngeal reflux

Background: Laryngopharyngeal reflux (LPR) is a highly prevalent disease and commonly encountered in the otolaryngologist’s office. Study to evaluate the presentation of different signs and symptoms of LPR along with evaluating the role of empiric PPI (proton pump inhibitor) in the management of LPR by observing its effect on RFS and RSI. Methods: A prospective observational study was conducted on 100 cases having different symptoms of LPR. Reflux symptom index (RSI) and Reflux finding score (RFS) were used to diagnose LPR. Patients were put on PPI (Pantoprazole 40 mg OD for 12 weeks) and followed up at 4,8 and 12 weeks and successive RSI and RFS scores were evaluated. The results were compiled and analyzed statistically. Results: Among all symptoms, most common presenting symptom of LPR was foreign body/sensation of something sticking in throat (80%). Upon pharmacological therapy with PPIs (Pantoprazole), the mean RSI score changed from 22.94±5.83 to 11.19±2.97 at 12 weeks of PPI therapy. The mean RFS score changed from 12.93±3.55 to 6.86±2.86 at 12 weeks of PPI therapy. The change in the RFS and RSI score was highly significant (p=0.001). Conclusions: LPR is a common condition presenting in ENT settings, the symptoms and signs of which may be complex. RFS and RSI score are valuable tools for diagnosing LPR. PPIs are proven to be effective therapy for LPR, more studies are encouraged to affirm the efficacy of PPIs over other management options.

REVISE: Re-Evaluating the Inhibition of Stress Erosions in the ICU: a randomised trial protocol

IntroductionThe Re-Evaluating the Inhibition of Stress Erosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding...

Pharmacological treatment of gastro-oesophageal reflux in children.

Pharmacological treatment of gastro-oesophageal reflux in children.

Effect of Long-Term Proton Pump Inhibitor Use on Blood Vitamins and Minerals: A Primary Care Setting Study.

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. 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. 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%, p < 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. 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.

Proton pump inhibitor-induced risk of chronic kidney disease is associated with increase of indoxyl sulfate synthesis via inhibition of CYP2E1 protein degradation

Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders in the gastrointestinal tract; however, PPI use increases the risk of chronic kidney disease (CKD) through unclear mechanisms. Considering that PPIs disturb the gut microbiome balance, which is involved in the precursor of gut-derived uremic toxin accumulation, and that gut-derived uremic toxins aggravate CKD progression, the aim of this study is to elucidate whether PPIs affect gut-derived uremic toxin metabolism, including indoxyl sulfate (IS), p-cresyl sulfate, and trimethylamine-N-oxide, as a mechanism for causing CKD. The present study showed that 3 week-treatment of PPIs (omeprazole, lansoprazole, and pantoprazole at 30 mg/kg) in mice only increased IS plasma levels among the above three gut-derived uremic toxins. Additionally, lansoprazole increased IS plasma concentrations along with increased exposure dose (7.5–30 mg/kg) and duration (1–3 weeks). However, nephrotoxicity with mild changes in glomerular structure and signs of fibrosis were observed only in groups exposed to a 3-week treatment of PPIs (30 mg/kg). As the concentrations of indole (the precursor of IS from gut metabolism) in the colon were only increased in the pantoprazole-treated group, the mechanism of increased IS exposure remains unclear. Further studies revealed that PPIs (omeprazole and lansoprazole; but not pantoprazole) increased IS production from indole in primary mouse hepatocytes in a concentration-dependent manner. Additionally, the increased protein levels of hepatic CYP2E1 (the key enzyme mediating IS formation) due to suppressed degradation resulted in an increase in IS levels. Although omeprazole and lansoprazole significantly inhibited IS uptake in hOAT1/3 in vitro, 3 weeks of PPI treatment did not reduce IS renal excretion in mice. In conclusion, PPIs induced IS synthesis via increased hepatic CYP2E1 protein level, subsequently leading to increased IS exposure. These findings present a plausible biological mechanism to explain the association of PPI use with the increased risk of CKD.

Drug Utilization Pattern Among Indoor Patients Treated Under CMAAY/PMJAY Insurance Schemes at Tertiary Care Hospital in Arunachal Pradesh, North East India

Background: Drug utilization pattern helps to understand the current trend of the drug used in various conditions by healthcare providers. It also helps in rationalizing budget expenditure on the medication cost. The Chief Minister Arogya Arunachal Yojana/Pradhan Mantri Jan Arogya Yojana (CMAAY/PMJAY) is a cashless scheme run by Govt of Arunachal Pradesh and Govt of India where the surgeries, medicines/surgical items cost are borne by the government. Present study assessed the drug utilization pattern among indoor patients treated under these insurance schemes. Material and Method: Retrospective cross-sectional study was conducted at Tomo Riba institute of Health and Medical Sciences (TRIHMS) in Arunachal Pradesh, North East India. Prescriptions of around 960 patients were analyzed who were treated from June 2020 to December 2020 (for 7 months) under above mentioned insurance schemes. Data was collected through the review of case sheets. For patients who have undergone surgery, the prescription on the post-operative day and for the patients managed conservatively, the prescription on the day of admission was analyzed. Information regarding Name, Age, Gender, Antimicrobial agents, Analgesics, Antiulcer drugs and other drugs given to the patients were collected. Results: A total of 960 patients were treated. 359 patients got benefitted in the insurance scheme by department of General surgery, 383 patients by dept of Obstetrics and Gynecology, 68 patients by orthopedics department, 65 patients by ENT dept, 85 patients by medicine department. Most common antimicrobial agent used were ceftriaxone (54.1%) followed by cefuroxime (17.5%) ,metronidazole (10%) and cefoperazone(7.5%). Some other antimicrobial agents preferred were piperacillin, tinidazole and amikacin. Most common antiulcer drug used was proton pump inhibitor pantoprazole (76.25%). The analgesics commonly used were diclofenac sodium (53.3%) followed by tramadol (30.6%), pentazocine (23.3%) and paracetamol (20.2%). Other drugs commonly used were ondansetron, butrophase and tranexemic acid. Conclusion: From our study, a conclusion can be withdrawn that if few of the antibiotics, analgesic, antiulcer drugs can be made available in the Govt set up through Govt procurement then the institute can work in more cost-effective and economical way.

Liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for determination of free and total dabigatran in human plasma and its application to a pharmacokinetic study

A high-performance liquid chromatography-tandem mass spectrometric method for the determination of free and total dabigatran in human plasma has been developed and validated using a stable labeled internal standard (IS) as dabigatran D4. The extraction of analyte and IS was accomplished by the solid-phase extraction technique. Chromatographic separations were achieved using Peerless basic C8 (150 × 4.6) mm, 5 µ column eluted at a flow rate of 1 mL/min with mobile phase Acetonitrile: 5 mM ammonium formate: Methanol and 0.2% formic acid (30:20:50, v/v/v). The run time of the method was about 2.5 min with elution times of dabigatran and dabigatran D4 at around 1.2 min. The multiple reaction monitoring transitions (Q1/Q3) were set at 472/289, 172 (m/z) for dabigatran, and 476/293 (m/z) for dabigatran D4. The calibration curves were linear (r 2 ≥0.99) over the range of 1.04–406.49 ng/mL. The presented method was successfully employed in the analysis of pharmacokinetic studies with the added advantage of demonstrating the effect of co-administration of dabigatran with the proton pump inhibitor pantoprazole on bioavailability and pharmacokinetic characteristics. Re-analysis of incurred sample resulted in >98% compliance indicating good assay precision of target analytes.

Association between migraine prevalence, treatment with proton-pump inhibitors and CYP2C19 phenotypes in UK Biobank

Proton-pump inhibitors (PPIs) are used to suppress gastric acid secretion in several gastrointestinal conditions. While these drugs are generally well tolerated, their long-term use may be associated with different adverse effects, including migraine. We analyzed the association between treatment with PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole) and migraine prevalence in the UK Biobank cohort through a cross-sectional analysis (using baseline data for 468,280 participants, 16,390 of whom had migraine) and a longitudinal analysis (including 145,007 participants with no migraine at baseline, of whom 3786 had probable migraine without aura [MWOA] and 9981 probable migraine with aura [MWA] or both MWOA and MWA at an average follow-up time of 10.06 years). We also evaluated the modulating role of the metabolizer phenotype of CYP2C19, the major enzyme involved in PPI clearance. Treatment with PPIs was associated with higher migraine prevalence at baseline (odds ratio [OR] = 1.25, p < 0.0001). CYP2C19 rapid metabolizer phenotype was associated with lower prevalence of migraine exclusively in participants treated with PPIs (OR = 0.89, p = 0.029). In addition, treatment with PPIs was associated with higher incidence of both probable MWOA (OR = 1.24, p = 0.002) and MWA (OR = 1.43, p < 0.0001) at follow-up. Treatment with PPIs and CYP2C19 poor metabolizer status were associated with higher incidence of probable chronic migraine exclusively in men. Our results suggest a significant association between treatment with PPIs and migraine in this large population-based cohort and support a potential relevant role of gender and CYP2C19 phenotype.

Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report.

Background: Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats.Objective: The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats.Methods: Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis.Results: Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 μg/mL, 0.8 h, and 0.2 hr*μg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study.Conclusion: The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.

ALTERATION OF PHARMACOKINETIC PARAMETERS OF PROTON PUMP INHIBITORS USING TRANSDERMAL DRUG DELIVERY SYSTEM

Objective: The present study was aimed to find out the effect of transdermal patches of proton pump inhibitors pantoprazole and esomeprazole on the alteration of pharmacokinetic parameters of these drugs. Methods: The transdermal patches were formulated by the solvent evaporation technique using polymers HPMC E5 with PVP K 30 and HPMC E5 with Eudragit L100 in different ratios. The best formulation from each of the drug pantoprazole and esomeprazole was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under the curve (AUC), area under first moment curve (AUMC), elimination rate constant (λz), biological half-life (t1/2), and mean residence time (MRT) were determined. Results: The plasma drug concentration vs time curve shows the extended-release of the drugs pantoprazole and esomeprazole when compared with the marketed formulation. The results show that there is no change in the peak plasma concentration, but a significant difference was observed in all the pharmacokinetic parameters. The AUC showed 6 fold increase for pantoprazole from 8.91 to 55.20 μg*h/ml and 3.5 fold increase for the drug esomeprazole from 7.86 to 28.53 μg*h/ml, and the mean residence time also showed 2 fold increase for the transdermal patches when compared with the marketed formulations. Conclusion: The increase in tmax, AUC, and MRT values of the formulated transdermal patches with the values of the marketed formulation of both the drugs, revealed that the transdermal patches can be used to deliver the drug for an extended period and also can alter the pharmacokinetics of pantoprazole and esomeprazole.

Do patients with gastroesophageal reflux disease exhibit compromised bone quality prior to proton pump inhibitor therapy?

Patients with gastroesophageal reflux disease (GERD) are routinely treated with proton pump inhibitors (PPIs), despite many reports of increased fracture risk associated with PPI use. Notably, the skeletal properties in patients with GERD prior to PPI therapy have not been addressed. We hypothesized that PPI-naïve GERD patients have bone impairment, and that short-term treatment with PPI has minimal skeletal effects. To test this, 17 (12 men/5 women) GERD patients age 32–73 years, not previously exposed to PPI, and 17 age- and sex-matched controls were enrolled from September 2010 to December 2012. Bone mineral density (BMD) at lumbar spine, femoral neck, total hip, and trabecular bone score (TBS) at the lumbar spine, a marker of bone microarchitecture, were measured by dual X-ray absorptiometry. Markers of bone turnover and calcium homeostasis, and gastric hormones were analyzed. The same parameters were measured after three months of treatment with the PPI pantoprazole. The GERD patients displayed a significantly lower TBS at baseline than controls (1.31 ± 0.11 vs. 1.43 ± 0.07, p = 0.0006). Total hip and femoral neck BMD were lower in patients compared to controls, however, not significantly (p = 0.09 and 0.12, respectively). CTX was non-significantly higher in GERD patients at baseline (p = 0.11). After three months, changes in BMD, TBS and CTX did not differ between the groups. In conclusion, this is the first report demonstrating compromised bone quality and inferior BMD in PPI-naïve GERD patients. Treatment with pantoprazole did not influence bone parameters, indicating that short-term use with this PPI is safe for the skeleton.

A141 SPONTANEOUS ESOPHAGEAL PERFORATION: AN UNREPORTED COMPLICATION OF LYMPHOCYTIC ESOPHAGITIS

Abstract Background Lymphocytic esophagitis is a new and rare clinicopathological entity. It is a histological pattern characterized by lymphocytic infiltrate without granulocytes. Its etiology and clinical significance remains unclear. The clinical manifestations are typically mild, with reflux and dysphagia the most commonly reported symptoms. Aims We describe a case report of spontaneous esophageal perforation associated with lymphocytic esophagitis. Methods Case report Results A previously well 31-year-old male presented to the emergency department with acute food impaction. His antecedent symptoms were acute chest discomfort and continuous odynophagia following his most recent meal, with persistent globus sensation. The patient had no reported history of allergies, atopy, rhinitis, or asthma. A previous history of non-progressive dysphagia was noted after resuscitation. Emergent endoscopy revealed no food bolus, but a deep 6 cm mucosal tear in the upper-mid esophagus extending 24 to 30 cm from the incisors. Chest computed tomography observed small volume pneumoperitoneum consistent with esophageal perforation. The patient’s recovery was uneventful; he was managed conservatively with broad-spectrum antibiotics, proton pump inhibitor therapy, and a soft-textured diet. Endoscopy was repeated 48 hours later and revealed considerable healing with only a residual 3-4cm linear laceration. Histology of biopsies taken from the mid and distal esophagus demonstrated marked infiltration of intraepithelial lymphocytes. There were no eosinophils or neutrophils identified, consistent with a diagnosis of lymphocytic esophagitis. Autoimmune indices including anti-nuclear antibodies and immunoglobulins were normal, ruling out a contributory autoimmune or connective tissue process. The patient was maintained on a proton pump inhibitor (pantoprazole 40 mg once daily) following discharge. Nearly six months following his presentation, the patient had a recurrence of symptoms prompting representation to the emergency department. He described acute onset chest discomfort while eating turkey. Computed tomography of the chest redemonstrated circumferential intramural gas in the distal esophagus and proximal stomach. Conclusions Esophageal perforation is a potentially life-threatening manifestation of what had been considered and described as a relatively benign condition. From isolated dysphagia to transmural perforation, this case significantly expands our current understanding of the clinical spectrum of lymphocytic esophagitis. Funding Agencies None

Эффективность комбинированной терапии больных эрозивной гастроэзофагеальной рефлюксной болезнью

Aim: to evaluate the efficacy and safety of combined therapy with a proton pump inhibitor (PPI) and an esophagoprotector to relieve the symptoms of reflux esophagitis, improve the life quality of patients and achieve faster and complete disease remission. Patients and Methods: a randomized study included 60 patients, including 33 men (mean age 40.96±13.44 years) and 27 women (mean age 48.29±12.69 years) with a duration of gastroesophageal reflux disease (GERD) of 21.85±15.48 months and C/D stage of reflux esophagitis. Depending on the prescribed treatment, the patients were divided into 2 groups of 30 subjects. Patients of the main group received complex therapy: PPI pantoprazole 40 mg once per day and esophagoprotector based on hyaluronic acid, chondroitin sulfate and poloxamer 407. In the comparison group, only pantoprazole was prescribed at the same dosage. The duration of the treatment course in both groups was 4 weeks. Before and after treatment, the presence and severity of complaints were assessed on the Likert scale, life quality according to the SF-36 questionnaire and endoscopic examination data. Results: after the end of the therapy course, a statistically significant decrease in the severity of epigastric burning, regurgitation, substernal pain, gaseous eructation, odynophagia and dysphagia was found both in the main group (in all cases p&lt;0.05, Wilcoxon Matched Pairs Test) and the comparison group (in all cases p&lt;0,05, Wilcoxon Matched Pairs Test). The use of combination therapy made it possible to achieve a more significant improvement in the life quality of patients in all indicators versus PPI monotherapy. In addition, 3 (10%) patients of the main group achieved endoscopic remission, while there were no such patients in the comparison group. The use of esophagoprotector in addition to PPI made it possible to reach the primary and secondary endpoints significantly more commonly versus during monotherapy. Conclusion: the obtained data indicate the high efficiency and safety of PPI therapy in combination with esophagoprotector for relieving the disease symptoms and improving the life quality of patients, faster and complete remission of reflux esophagitis by additional restoration of the esophageal mucosa resistance. Esophagoprotector as a component of complex therapy together with PPI allows achieving clinical and endoscopic disease remission in patients with erosive esophagitis in shorter terms. KEYWORDS: gastroesophageal reflux disease, esophageal mucosa resistance, esophagoprotection, proton pump inhibitor, quality of life. FOR CITATION: Matoshina I.V., Livzan M.A., Fedorin M.M., Lapteva I.V. Efficacy of combined therapy in patients with erosive gastroesophageal reflux disease. Russian Medical Inquiry. 2021;5(6):366–372 (in Russ.). DOI: 10.32364/2587-6821-2021-5-6-366-372.

Pantoprazole impairs fracture healing in aged mice

Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation.

Use of Proton Pump Inhibitors in Saudi Arabia: A Cross-Sectional Retrospective Drug Utilization Study

Objective: Chief aim of the current study was to draw attention in the prescribing pattern and utilization of PPIs in one year at a single private hospital of Saudi Arabia.&#x0D; Methods: This is a cross-sectional, retrospective drug utilization research on Proton pump inhibitors (PPIs). The PPI usage pattern of in- and out- patients of Al-Mana Group of Hospital (AGH) Al-Khobar between January 1, 2019 and December 31, 2019 were investigated, including incidence, prevalence, and duration.&#x0D; Results: We observed 27229 items of PPI were dispensed in the inpatient and outpatient pharmacy department of AGH-Al-khobar. Among all the PPI user more than the half {(52.98%, n = 14426), 95%CI (52.0-53.5)} were male. Nearly equal number of PPI users belongs between 18-40 years {(39.22%, n =10680), 95%CI (38.64-39.80)} and 41-60 years {(39.15%, n =10662), 95%CI (38.6-39.75)}. Among all the PPI users 61.46% (n=16736) were from community of Saudi Arabia while 38.53% (n=10493) from Non-Saudi. Among all the dispensed PPIs drugs Pantoprazole is dispensed to the highest number of patients {79% (95%CI, 78.53-79.50) (n=21515), p&lt;0.05} while their average duration of therapy was 18.78 days. All the PPI prescribed to the AGH-Al-khobar patients adhere to the NICE guideline (p-value &lt;0.05).&#x0D; Conclusions: We also observed that PPIs was prescribed in AGH Al-khobar adhere to clinical guidelines. In our study among all the PPI Pantoprazole was prescribed to the highest number of patients, hence their safe and effective use must be warranted.

A retrospective study on prescribing pattern and cost analysis of proton-pump inhibitors used among adults of Saudi Arabia

Abstract Objective To evaluate the use of proton-pump inhibitors (PPIs) for treatment of different gastric disease in Saudi population and their related administration cost. Materials and methods It was a cross-sectional retrospective drug utilization study. The utilization rates and cost analysis of each PPIs class of drugs were compared. Study data were obtained from pharmacy database. Data between 1 January 2019 and 31 December 2019 were investigated, including incidence, prevalence and duration of use of proton-pump inhibitors among adults of Saudi Arabia. Key findings We observed 26 798 (4.27%) prescription of PPIs were dispensed in the in-patient and out-patient pharmacy department of Al-Mana Group of Hospital (AGH) Al khobar. Among all the PPIs user, more than the half ((53.01%, n = 14 208), 95% CI (52.42–53.62)) were male. 30–40 years age patients (24.57%, 95% CI (24.06–25.09) (n = 6585)) were highest number of PPI users. Nearly, equal number of PPI users belongs between 51–60 years ((20.88%, n = 5596), 95% CI (20.40–21.37)) and &amp;gt;60 years ((20.36%, n = 5456), 95% CI (19.8–20.85)). Among all the dispensed PPIs drugs, Pantoprazole is dispensed to the highest number of patients (79.09% (95% CI, 78.61–79.58) (n = 21 197)) while their average duration of therapy was 18.86 days. Among all PPIs, pantoprazole average unit wise cost was highest SR 8.83 (USD 2.35) in comparison to other PPIs. Conclusion In our study, among all the PPIs Pantoprazole was prescribed to the highest number of patients also it was costliest; hence, their safe and effective use must be warranted. Current study will also help in to develop nation database regarding utilization of proton-pump inhibitors.