Preliminary Study of Gastroprotective Effect of Aloe perryi and Date Palm Extracts on Pyloric Ligation-Induced Gastric Ulcer in Experimental Rats.

OBJECTIVE: The present study was aimed at investigating the possible antiulcer activities of some natural phytochemicals Aloe perryi leaf extract (APLE) and flower extract (APFE) in addition to the date palm seed extract (DPSE) and the oily samples of DPSE in a pylorus ligation-induced ulcer model using ranitidine as a standard antiulcer drug. BACKGROUND: Peptic ulcer is a prevalent gastrointestinal disorder due to hypersecretion of gastric acid. It affects four million people worldwide, and 2-10% of these ulcers are perforated and cause bleeding. This increases the risk of morbidity and mortality. So we aimed to introduce a primary study alternatively safe method for treating peptic ulcer. MATERIALS AND METHODS: Forty-two Wistar Albino rats of either sex were randomly divided into seven groups (6/each). The pylorus ligation was done to induce ulcer in pretreated albino rats. The antiulcer activities of extracts were estimated at different dose levels (250 and 500 mg/kg) using ranitidine as a standard drug (50 mg/kg). Gastric volume, pH, and total and free acidity as well as ulcer index and percentage of ulcer inhibition were measured to elucidate the antiulcerogenic effects. Histological examination of gastric ulcer was also performed. Statistical analysis for the results was done where P < 0.05 was considered statistically significant. RESULTS: Pylorus ligation for 6 h in control rats resulted in gastric ulcer which was indicated by the accumulation of gastric secretion and increased total acidity and decreased pH. The pretreatment of rats with APLE, APFE, and DPSE in addition to the oily samples of DPSE significantly inhibited the ulcers induced by pylorus ligation. These effects were attributed to significant reductions in total and free acidity, ulcer index, and gastric volume while there is a marked decrease in gastric pH (the antisecretory) as well as mucosal strengthening properties of these phytochemicals. CONCLUSION: These findings give these extracts the potential to be a promising tool for the management of gastric ulcer after performing further clinical and experimental studies. Our study demonstrated the promising antiulcer activity of extracts and oils in pyloric ligation-induced gastric ulcer. To the best of our knowledge, this is the first study to explore the antiulcer activity of these extracts; however, further investigations may be recommended for full details about this antiulcerogenic capacity.

Using in vitro ADME data for lead compound selection: An emphasis on PAMPA pH 5 permeability and oral bioavailability.

Membrane permeability plays an important role in oral drug absorption. Caco-2 and Madin-Darby Canine Kidney (MDCK) cell culture systems have been widely used for assessing intestinal permeability. Since most drugs are absorbed passively, Parallel Artificial Membrane Permeability Assay (PAMPA) has gained popularity as a low-cost and high-throughput method in early drug discovery when compared to high-cost, labor intensive cell-based assays. At the National Center for Advancing Translational Sciences (NCATS), PAMPA pH 5 is employed as one of the Tier I absorption, distribution, metabolism, and elimination (ADME) assays. In this study, we have developed a quantitative structure activity relationship (QSAR) model using our ∼6500 compound PAMPA pH 5 permeability dataset. Along with ensemble decision tree-based methods such as Random Forest and eXtreme Gradient Boosting, we employed deep neural network and a graph convolutional neural network to model PAMPA pH 5 permeability. The classification models trained on a balanced training set provided accuracies ranging from 71% to 78% on the external set. Of the four classifiers, the graph convolutional neural network that directly operates on molecular graphs offered the best classification performance. Additionally, an ∼85% correlation was obtained between PAMPA pH 5 permeability and in vivo oral bioavailability in mice and rats. These results suggest that data from this assay (experimental or predicted) can be used to rank-order compounds for preclinical in vivo testing with a high degree of confidence, reducing cost and attrition as well as accelerating the drug discovery process. Additionally, experimental data for 486 compounds (PubChem AID: 1645871) and the best models have been made publicly available (https://opendata.ncats.nih.gov/adme/).

Ranitidine Use and Risk of Upper Gastrointestinal Cancers.

BACKGROUND: The discovery that ranitidine is contaminated with N-nitrosodimethylamine, a suspected human carcinogen, raises the hypothesis of a gastrointestinal carcinogenic effect; however, evidence remains inconclusive. METHODS: We used the nationwide Danish Prescription Registry to identify a cohort of incident ranitidine users and two active comparator cohorts comprising users of other histamine-2 receptor blockers (H2RB) and users of proton pump inhibitors (PPI). All Danish adults with a first prescription of ranitidine, other H2RBs, or PPIs in 1996 through 2008 were followed virtually completely through 2018 for incidence of esophageal, stomach, liver, and pancreatic cancers. We used Cox regression with propensity-score weighting to calculate hazard ratios and 10-year cumulative risk with 95% confidence intervals. RESULTS: We ascertained 276 newly diagnosed esophageal, 342 stomach, 133 hepatocellular, and 517 pancreatic cancers among ranitidine users during follow-up (median 14 years). In comparison with use of other H2RBs or PPIs, we found no consistent evidence of increased HRs or excess 10-year cumulative risk of any upper gastrointestinal cancer following ranitidine use. We observed no association after restriction to subjects with at least 5 or 10 prescriptions or those with 10 prescriptions and at least 10 years of follow-up. CONCLUSIONS: Our large prospective study using high-quality prescription and cancer incidence data, with two active comparator groups, provides no compelling evidence that ranitidine increases the risk of upper gastrointestinal cancers. IMPACT: Our results, which do not support any carcinogenic effect on esophagus, stomach, liver or pancreas, should be reassuring for millions of concerned past users of ranitidine.

Pretreatment with Ranitidine Bismuth Citrate May Improve Success Rates of Helicobacter pylori Eradication: A Prospective, Randomized, Controlled and Open-Label Study.

Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.

Effect of Oral Ranitidine on Urinary Excretion of N-Nitrosodimethylamine (NDMA): A Randomized Clinical Trial.

Importance: In 2019, the US Food and Drug Administration (FDA) received a citizen petition indicating that ranitidine contained the probable human carcinogen N-nitrosodimethylamine (NDMA). In addition, the petitioner proposed that ranitidine could convert to NDMA in humans; however, this was primarily based on a small clinical study that detected an increase in urinary excretion of NDMA after oral ranitidine consumption. Objective: To evaluate the 24-hour urinary excretion of NDMA after oral administration of ranitidine compared with placebo. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) conducted in 18 healthy participants. The study began in June 2020, and the end of participant follow-up was July 1, 2020. Interventions: Participants were randomized to 1 of 4 treatment sequences and over 4 periods received ranitidine (300 mg) and placebo (randomized order) with a noncured-meats diet and then a cured-meats diet. The cured-meats diet was designed to have higher nitrites, nitrates (nitrate-reducing bacteria can convert nitrates to nitrites), and NDMA. Main Outcome and Measure: Twenty-four-hour urinary excretion of NDMA. Results: Among 18 randomized participants (median age, 33.0 [interquartile range {IQR}, 28.3 to 42.8] years; 9 women [50%]; 7 White [39%], 11 African American [61%]; and 3 Hispanic or Latino ethnicity [17%]), 17 (94%) completed the trial. The median 24-hour NDMA urinary excretion values for ranitidine and placebo were 0.6 ng (IQR, 0 to 29.7) and 10.5 ng (IQR, 0 to 17.8), respectively, with a noncured-meats diet and 11.9 ng (IQR, 5.6 to 48.6) and 23.4 ng (IQR, 8.6 to 36.7), respectively, with a cured-meats diet. There was no statistically significant difference between ranitidine and placebo in 24-hour urinary excretion of NDMA with a noncured-meats diet (median of the paired differences, 0 [IQR, -6.9 to 0] ng; P = .54) or a cured-meats diet (median of the paired differences, -1.1 [IQR, -9.1 to 11.5] ng; P = .71). No drug-related serious adverse events were reported. Conclusions and Relevance: In this trial that included 18 healthy participants, oral ranitidine (300 mg), compared with placebo, did not significantly increase 24-hour urinary excretion of NDMA when participants consumed noncured-meats or cured-meats diets. The findings do not support that ranitidine is converted to NDMA in a general, healthy population. Trial Registration: ClinicalTrials.gov Identifier: NCT04397445.

The Effects of Ranitidine Treatment on the Risk of Necrotizing Enterocolitis in Preterm Infants: A Case-Control Study.

INTRODUCTION: Gastric acidity plays an important role in the protection of infants against various pathogens from the environment. The histamine-2 receptor blockers (H2-blockers) are off-labeled drugs that are frequently prescribed in preterm neonates to prevent stress ulcers. The impact of the H2-blockers on the development of the necrotizing enterocolitis (NEC) in preterm infants is still controversial, particularly in the developing world. MATERIALS AND METHODS: One hundred twenty-two preterm infants were enrolled in the study. The multivariate logistic regression model was used to identify potential postnatal risk factors associated with NEC. RESULTS: Preterm infants (n = 51) with total NEC, medical NEC, and surgical NEC had the highest rate of receiving ranitidine compared with controls (n = 71) (39.2%, 19.6%, and 47.6%, p < 0.05). Logistic regression analysis revealed that ranitidine use and nosocomial infections were significantly associated with NEC development (odds ratios 1.55 and 3.3). CONCLUSIONS: We confirm that ranitidine administration was associated with an increased risk of NEC in preterm infants. H2-blockers use should be only administered in very strictly selected cases after careful consideration of the risk-benefit ratio.

The added value of H2 antagonists in premedication regimens during paclitaxel treatment.

BACKGROUND: Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine. METHODS: This prospective, pre-post interventional, non-inferiority study compared the standard premedication regimen (N = 183) with dexamethasone, clemastine and ranitidine with a premedication regimen without ranitidine (N = 183). The primary outcome was the incidence of HSR grade ≥3. Non-inferiority was determined by checking whether the upper bound of the two-sided 90% confidence interval (CI) for the difference in HSR rates excluded the +6% non-inferiority margin. RESULTS: In both the pre-intervention (with ranitidine) and post-intervention (without ranitidine) group 183 patients were included. The incidence of HSR grade ≥3 was 4.4% (N = 8) in the pre-intervention group and 1.6% (N = 3) in the post-intervention group: difference -2.7% (90% CI: -6.2 to 0.1). CONCLUSIONS: As the upper boundary of the 90% CI does not exceed the predefined non-inferiority margin of +6%, it can be concluded that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine. CLINICAL TRIAL REGISTRATION: www.trialregister.nl ; NL8173.

The effect of ranitidine administration in graded dosage to the degree of liver damage: A study on Wistar rats with acute methanol intoxication.

The high incidence of alcoholic poisoning in Indonesia is caused by the use of methanol as a surrogate ingredient of nonconforming alcohol. The product of methanol metabolism is toxic to the liver. Ranitidine has been studied as an antidote to reduce the effect of methanol toxicity. The present study aimed to assess the effect of ranitidine administration on the liver damage of Wistar rats with acute methanol intoxication. This research was an experimental study with randomized and posttest-only control group design. A total of 24 male Wistar rats divided into four groups, each consisting of six Rats. The control group (K0) served as a reference normal value. The control group (K1) was intoxicated with methanol 7 g/kg body weight (b.w.) through rat gavage tube. Treatment groups were intoxicated with methanol and 15 minutes after that, Ranitidine (30 mg/kg b.w. (P1) or 60 mg/kg b.w. (P2)) was given intraperitoneally. Ranitidine administration was proven to protect the liver tissue from damage due to methanol intoxication as was indicated from the histopathological examination. Ranitidine with dose 60 mg/kg b.w. is better in reducing the degree of liver tissue damage in acute methanol intoxication rats.

How often we diagnose allergy to ranitidine?

H2 receptors' antagonists (H2RA) are widely used drugs and they are generally well-tolerated. Ranitidine hypersensitivity reactions (HR) are rarely reported. The article emphasizes the importance of recognizing ranitidine as a cause of anaphylaxis and the advantages and limits of allergological evaluation to establish a positive diagnose. We reviewed a series of published cases of ranitidine-induced hypersensitivity reactions, starting from a clinical case presentation. Moreover, we analyzed the ranitidine related adverse events in the Eudravigilance European database of adverse reactions. Most of the allergic reactions induced by ranitidine are type I HR with immediate onset after exposure, with variable clinical presentation. But in a few cases, there were also described delayed reactions, some after occupational exposure. The article underlines the importance of allergy evaluation to avoid future contact with the drug to reduce the risk of more severe reactions. The suspected reactions should be reported, allowing pharmacovigilance systems to analyse them and to establish further recommendations for clinicians.

Consistent gastric pH-dependent effects of suppressors of gastric acid secretion on the antihypertensive responses to oral nitrite.

Proton pump inhibitors (PPI) are suppressors of gastric acid secretion (SGAS) that decrease gastric nitric oxide (NO) formation from nitrite and increase the cardiovascular risk. However, H2 receptor antagonists (H2RA) are considered safer than PPIs. We challenged this notion and hypothesized that both omeprazole (PPI) and ranitidine (H2RA) attenuate the responses to oral nitrite because both drugs increase gastric pH and therefore could decrease nitrite-derived NO formation in the stomach. We examined the blood pressure responses to oral nitrite in hypertensive rats treated with omeprazole, ranitidine, or vehicle. Chemiluminensce-based assays were used to measure gastric NO formation, plasma and gastric concentrations of nitrite, nitrate, and nitrosylated species (RXNO) to clarify the mechanism involved in the effects of SGAS on the responses to oral nitrite. Both drugs increased gastric pH, impaired oral nitrite-induced hypotensive responses, gastric NO formation, and blunted the increases in circulating RXNO concentrations, but not in circulating nitrite and nitrate concentrations. These findings were reproduced in a second study using sodium acetate buffers at pH 3.5, 4.5, and 5.5 to mimic gastric pH found with vehicle, ranitidine, and omeprazole, respectively. Increasing gastric pH impaired oral nitrite-induced hypotensive responses, gastric NO formation, and blunted the increases in circulating RXNO concentrations, but not in circulating nitrite and nitrate concentrations. Our results clearly indicate that SGAS impair nitrite-induced gastric formation of NO and vasoactive RXNO in a pH-dependent manner, thus resulting in impaired responses to oral nitrite. These findings may have several clinical implications, particularly to patients with cardiovascular diseases.

Pharmacokinetic Drug-Drug Interactions Between Trospium Chloride and Ranitidine Substrates of Organic Cation Transporters in Healthy Human Subjects.

Trospium chloride, a muscarinic receptor blocker, is poorly absorbed with different rates from areas in the jejunum and the cecum/ascending colon. To evaluate whether organic cation transporter (OCT) 1, OCT2 and multidrug and toxin extrusion (MATE) 1 and MATE2-K are involved in pharmacokinetics, competitions with ranitidine, a probe inhibitor of the cation transporters, were evaluated in transfected HEK293 cells. Furthermore, a drug interaction study with trospium chloride after intravenous (2 mg) and oral dosing (30 mg) plus ranitidine (300 mg) was performed in 12 healthy subjects and evaluated by noncompartmental analysis and population pharmacokinetic modeling. Ranitidine inhibited OCT1, OCT2, MATE1, and MATE2-K with half maximal inhibitory concentration values of 186 ± 25 µM, 482 ± 105 µM, 134 ± 37 µM, and 35 ± 11 µM, respectively. In contrast to our hypothesis, coadministration of ranitidine did not significantly decrease oral absorption of trospium. Instead, renal clearance was lowered by ∼15% (530 ± 99 vs 460 ± 120 mL/min; P < .05). It is possible that ranitidine was not available in competitive concentrations at the major colonic absorption site, as the inhibitor is absorbed in the small intestine and undergoes degradation by microbiota. The renal effects apparently result from inhibition of MATE1 and/or MATE2-K by ranitidine as predicted by in vitro to in vivo extrapolation. However, all pharmacokinetic changes were not of clinical relevance for the drug with highly variable pharmacokinetics. Intravenous trospium significantly lowered mean absorption time and relative bioavailability of ranitidine, which was most likely caused by muscarinic receptor blocking effects on intestinal motility and water turnover.

Swellable and porous bilayer tablet for gastroretentive drug delivery: Preparation and in vitro-in vivo evaluation.

The purpose of this study was to develop a novel gastroretentive drug delivery system with immediate buoyancy and high wet strength. The proposed bilayer tablet was composed of a drug layer and a highly porous and swellable gastroretentive (GR) layer. The highly porous GR layer was prepared by sublimating the volatile materials after compaction with swellable polymers. This pore-forming process decreased the density of the GR layer and enabled the tablet to float immediately on the dissolution media. The GR layer formulation was optimized by comparing the swelling, erosion, and mechanical properties of candidate swellable polymers. The release rates were conveniently controlled by changing the polymer content in the drug layer, while the swelling and floating properties were provided by the GR layer. The application of percolation theory revealed that the polymer content above the estimated threshold was required for a reliable drug release profile. In vivo study in fed beagle dogs confirmed the enhanced gastric retention time of the tablets compared to that of conventional single layer tablets. Taken together, our data suggest that the proposed system can be a promising platform technology with superior GR properties and a convenient formulation process.

The effects of vitamins and selenium mixture or ranitidine against small intestinal injury induced by indomethacin in adult rats.

This study was aimed at investigating morphological and biochemical efficacies of antioxidants on indomethacin-induced small intestinal damage in rats. Group I: control animals (negative control) given only placebo, Group II: (positive control) are animals orally given combination of antioxidants [vitamin C (Vit C), vitamin E (Vit E), ß-carotene and sodium selenite (Se)] daily for 3 days, Group III: Rats were given only indomethacin, Group IV: animals were given of antioxidants combination for 3 days, last dose was given 2 hr before the administration of indomethacin. Group V: Animals receiving ranitidine for 3 days (second positive control). Group VI: Animals received ranitidine for 3 days, last dose was given 2 hr before to indomethacin administration. Indomethacin caused degenerative morphological and biochemical changes, which were reversed on antioxidants administration. As a result, we propose that antioxidants combination would be therapeutically beneficial for treating indomethacin-induced lesions of small intestine. PRACTICAL APPLICATIONS: Indomethacin is a widely preferred nonsteroidal anti-inflammatory drug (NSAID) but its side effects on gastrointestinal system are well known. Indomethacin also causes production of reactive oxygen species. Antioxidants and selenium has protective effects. According to the results of this study, antioxidants and selenium can be used as a food supplement for preventing NSAID-induced side effects and toxicity.

The histaminergic control of the iridal vascular tone in rats and its influencing by topical administration of olopatadine and ranitidine.

Objective. We evaluated the histamine's role in regulating the iris vasomotricity in rats, using as a research tool topical olopatadine, a selective H1 blocker, which is indicated for the treatment of allergic conjunctivitis and ranitidine, a selective H2 blocker mainly used for the treatment of peptic ulcer disease. Methods. Two groups of six Wistar rats anesthetized with ketamine 200 mg/kg body weight were used. They received distilled water in conjunctival instillations, initially and after 5 minutes, olopatadine 2.5 mmol/ l for the first group, respectively ranitidine 2.5 mmol/ l for the second group. The changes of the iris arteriolar and venular diameters were recorded. Results. Both olopatadine and ranitidine produced statistically significant iridal arteriolar vasoconstriction and ranitidine determined statistically significant venuloconstriction, while distilled water did not produce any statistically significant effect. Conclusions. There is a vasodilator histaminergic tone exerted through the histaminergic H1 and H2 receptors in the iris arterioles and, respectively, through the H2 receptors in the iridal venules. Olopatadine, a topical H1 antagonist used in the treatment of ocular allergies, may interfere with the humoral regulation of the iris arteriolar tone. Ranitidine, an H2 antagonist, decreased the diameter of the iris arterioles and venules, when administered topically in rats.

Pylera® plus ranitidine vs Pylera® plus esomeprazole in first-line treatment of Helicobacter pylori infection: Two pilot studies.

BACKGROUND: Several studies have shown that Pylera® (three-in-one capsules containing 140 mg bismuth potassium subcitrate, 125 metronidazole, and tetracycline 125 mg) in association with omeprazole or esomeprazole is a good option in the treatment of Helicobacter pylori infection. In particular, the adjunction of a PPI to Pylera® may be useful to overcome metronidazole resistance. However, omeprazole and its derivatives can promote greater bismuth absorption and enhance its toxicity. The H2 receptor antagonist (H2RA) ranitidine seems to induce less bismuth absorption and as a consequence less systemic toxicity. AIM: To evaluate whether Pylera® in combination with esomeprazole or with ranitidine is equally effective in the treatment of H. pylori infection. MATERIAL AND METHODS: Two separate groups of patients were treated simultaneously. One group was treated with Pylera® three capsules qid plus esomeprazole 40 mg bid for 10 days (group A), and the other group was treated with Pylera® three capsules qid plus ranitidine 300 mg bid for 10 days (group B). H. pylori eradication was defined as a negative result in 13 C urea breath test performed at least 8 weeks after the end of treatment with a delta-over-baseline value less than 5. RESULTS: Thirty-two patients were recruited for group A and thirty-three patients in group B. Eradication rates were 93.7% (30/32) and 90.9% (30/33), respectively, at intention-to-treat analysis, and 96.6% (29/30) and 93.3% (28/30), respectively, at per-protocol analysis. Adverse events occurred in 26 patients and led to the suspension of treatment in one patient in group A and in one patient in group B. CONCLUSION: The results showed that Pylera® plus a PPI or ranitidine were equally effective in the population studied. The high cure rates of bismuth triple therapy (without an antisecretory drug) and the lack of susceptibility testing make it impossible to exclude the possibility that the results would have been similar if neither the PPI nor the ranitidine were given.

Oil-entrapped ranitidine HCl beads heal peptic ulcers via local and systemic mechanisms.

OBJECTIVE: Oral gastroretentive system is one of the site-specific drug delivery system, which is designed to be retained in upper GIT for a prolonged time. Ranitidine hydrochloride (RHCl), which is used frequently in treatment of peptic ulcer, is a suitable candidate for gastroretentive delivery systems. Dependently, floating oil-entrapped alginate beads of RHCl were developed and evaluated as an approach to site-specific delivery avoiding colonic degradation and enhancing both bioavailability and the proposed local effect. METHODS: Different formulations of floating beads were suggested and randomized using 24 full factorial design. Optimized formulation was subjected for in vivo studies to measure the oral bioavailability and the healing effect of induced peptic ulcers. RESULTS: Beads size ranged from 1.32 to 2.3 mm. All beads revealed excellent floating capabilities. Optimum formulation (F12) has entrapment efficiency of 70%, drug loading of 7% and 71% RHCl released after 6 h. SEM of F12 shows a grossly spherical structure with presence of oil droplets distributed throughout structure. AUC obtained from F12 was nonsignificantly higher than that of a commercial tablet. Signs of ulcer healing appeared clearly with F12 through appearance of granulation tissue, collagen fibers and newly formed blood vessels. Healing rate and extent obtained with a commercial tablet were less than F12. Quantitative analysis confirmed histopathological findings. CONCLUSION: Floating oil-entrapped beads are a promising approach for RHCl delivery to remain in stomach for a longer time ensuring site-specific delivery and consequently, enhancing local healing effect of peptic ulcers.

Reduction in ocrelizumab-induced infusion reactions by a modified premedication protocol.

BACKGROUND: Ocrelizumab is a monoclonal antibody directed against CD20+ B cells that is approved for MS. The most common side effect is infusion-associated reactions (IARs). This study examines whether a modified premedication protocol reduces incidence of IARs and further examines predictors of IARs. METHODS: Patients took cetirizine 10 mg, ranitidine 75 mg, and increased hydration the night before the ocrelizumab infusion. This regimen was repeated the next day prior to arrival. Just prior to the infusion, patients were pretreated with IV diphenhydramine 50 mg, IV methylprednisolone 125 mg, and oral acetaminophen 650 mg. Rates of IARs with this modified protocol were compared to patients who had received only pretreatment medications. RESULTS: 207 patients received ocrelizumab. With the modified premedication protocol, we found significant decreased odds of IARs (OR 0.40, p = 0.024, 95% CI (0.18, 0.88). Among the baseline characteristics, there was a significant reduction of IARs with increasing age (OR 0.94, p = 0.001) and male sex (OR 0.34, p = 0.034). Body mass index (BMI) increased the odds of IARs (OR 1.07, p = 0.029). Race and smoking status did not affect IARs. CONCLUSION: The modified premedication protocol described herein significantly decreases rates of IARs by 60% and suggests that the additional premedication regimen is beneficial. Age and male sex are protective for IARs while BMI is a risk factor for IARs.

[Pharmaceutical prescription of proton pump inhibitors and ranitidine in the general population living in the area of the Healthcare Authority and University of Udine (Friuli Venezia Giulia, Northeastern Italy)]. / La prescrizione farmaceutica territoriale di inibitori di pompa protonica e ranitidina nella popolazione residente nell'area della Azienda sanitaria universitaria integrata di Udine.

OBJECTIVES: to describe the use of proton pump inhibitors (PPI) and ranitidine in the general population living in the area of the Healthcare Authority and University of Udine (Friuli Venezia Giulia, Northeastern Italy) and to evaluate whether there are any cases of co-prescription of medications in those classes. DESIGN: analysis of health-related administrative databases (list of potential healthcare beneficiaries, prescriptions of medications, exemption from medical charges because of chronic conditions, list of general practitioners). SETTING AND PARTICIPANTS: population of the Italian area of the Healthcare Authority and University of Udine (approximately 250,000 inhabitants) ≥1 year of age as of January 1st, 2016. MAIN OUTCOME MEASURES: prevalence of PPI or H2RA use (>1 prescription in 2016), overall and stratified by drug, age class and sex; duration of the theoretical period covered by prescriptions; prevalence of co-prescriptions; association of co-prescriptions and clinical and demographic characteristics of patients (odds ratio and 95% confidence intervals). RESULTS: in 2016, 162 persons per 1,000 used those medications; in particular, 158/1,000 used PPIs. Prevalence of use increased with age, as did the median treatment duration with PPIs. Co-prescription of two medications of the same class were observed in 0.43% of antacid users. The likelihood of receiving co-prescriptions was higher among non-elderly subjects, long-term PPI users, and those with chronical diseases, such asthma. CONCLUSION: in the considered Italian area, PPIs and ranitidine were frequently used, although less than in the rest of Italy. We observed occasionally non-recommended practices, such as the co-prescription of different medications of the same class or with the same indications.