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Alimentary Pharmacology & Therapeutics Apr 2009Dexlansoprazole MR employs a dual delayed-release delivery system that extends drug exposure and prolongs pH control compared with lansoprazole. (Randomized Controlled Trial)
Randomized Controlled Trial
Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation--results from two randomized controlled studies.
BACKGROUND
Dexlansoprazole MR employs a dual delayed-release delivery system that extends drug exposure and prolongs pH control compared with lansoprazole.
AIM
To assess the efficacy and safety of dexlansoprazole MR in healing erosive oesophagitis (EO).
METHODS
Patients in two identical double-blind, randomized controlled trials (n = 4092) received dexlansoprazole MR 60 or 90 mg or lansoprazole 30 mg once daily. Week 8 healing was assessed using a closed testing procedure--first for non-inferiority, then superiority, vs. lansoprazole. Secondary endpoints included week 4 healing and week 8 healing in patients with moderate-to-severe disease (Los Angeles Classification grades C and D). Life-table and crude rate analyses were performed. Symptoms and tolerability were assessed.
RESULTS
Dexlansoprazole MR achieved non-inferiority to lansoprazole, allowing testing for superiority. Using life-table analysis, dexlansoprazole MR healed 92-95% of patients in individual studies vs. 86-92% for lansoprazole; the differences were not statistically significant (P > 0.025). Using crude rate analysis, dexlansoprazole MR 90 mg was superior to lansoprazole in both studies and 60 mg was superior in one study. Week 4 healing was > 64% with all treatments in both studies. In an integrated analysis of 8-week healing in patients with moderate-to-severe EO, dexlansoprazole MR 90 mg was superior to lansoprazole. All treatments effectively relieved symptoms and were well tolerated.
CONCLUSION
Dexlansoprazole MR is highly effective in healing EO and offers benefits over lansoprazole, particularly in moderate-to-severe disease.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Aged, 80 and over; Delayed-Action Preparations; Dexlansoprazole; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis; Female; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome; Young Adult
PubMed: 19183157
DOI: 10.1111/j.1365-2036.2009.03933.x -
Alimentary Pharmacology & Therapeutics Feb 2011Dexlansoprazole MR is a Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to extend the duration of acid suppression. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Dexlansoprazole MR is a Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to extend the duration of acid suppression.
AIM
To assess the 12-month safety of dexlansoprazole MR in patients with symptomatic gastro-oesophageal reflux disease (GERD).
METHODS
In this randomised open-label study, patients received dexlansoprazole MR 60 or 90 mg once-daily for 12 months. Safety was evaluated at months 1, 3, 6, 9 and 12/final visit through physical examinations, laboratory evaluations, endoscopies, gastric biopsies, fasting serum gastrin values and adverse events (AEs).
RESULTS
Of 591 patients receiving dexlansoprazole MR 60 and 90 mg, 71% and 65%, respectively, experienced ≥1 treatment-emergent AE; the most frequent AE was upper respiratory infection (14% and 13% in the 60- and 90-mg groups). Thirty patients experienced ≥1 serious AE; a majority of serious AEs were unrelated to study drug. No clinically meaningful change in any clinical laboratory parameters was noted. As expected, serum gastrin values rose with dexlansoprazole therapy; increases were not dose related. No clinically concerning trends were identified in gastric pathology results; no endocrine cell hyperplasia, adenocarcinoma, or lymphoma were observed.
CONCLUSIONS
Twelve-month treatment with dexlansoprazole MR 60 and 90 mg was well tolerated by GERD patients in this study (Clinicaltrials.gov identifier NCT00255190).
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Delayed-Action Preparations; Dexlansoprazole; Dose-Response Relationship, Drug; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Statistics as Topic; Time Factors; Treatment Outcome; Young Adult
PubMed: 21118280
DOI: 10.1111/j.1365-2036.2010.04519.x -
Indian Journal of Pharmacology 2020Levofloxacin-based triple therapies are considered the standard regimen for eradication of Helicobacter pylori (H. pylori) due to decreased sensitivity to clarithromycin... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Levofloxacin-based triple therapies are considered the standard regimen for eradication of Helicobacter pylori (H. pylori) due to decreased sensitivity to clarithromycin and the optimal duration of therapy is still controversial. Besides, there is no complete evidence about dexlansoprazole efficacy in the eradication of H. pylori.
AIM
Our study aimed to determine the effectiveness of triple therapy based on levofloxacin-dexlansoprazole as a standard treatment for H. pylori infection and estimate the effect of H. pylori on lipid profile and hemoglobin (Hb).
MATERIALS AND METHODS
A pilot prospective randomized trial of a triple therapy based on levofloxacin-dexlansoprazole for H. pylori eradication was conducted at Damanhour Medical National Institute, Egypt; 66 participants with H. pylori infection received levofloxacin (500 mg/day) plus amoxicillin (1 g/12 h) plus dexlansoprazole (60 mg/day). All medications administrated orally for either 7 days or 10 days. Four weeks after treatment, the eradication was assessed by the stool antigen test.
RESULTS
The rate of eradication was 63.6% in levofloxacin, amoxicillin, and dexlansoprazole (LAD) 7-day group, and 90.9% in LAD 10-day group. In addition, laboratory test results showed a significant difference in Hb, low-density lipoprotein, high-density lipoprotein, triglyceride, and total cholesterol levels before and after treatment (P < 0.05).
CONCLUSION
LAD 10 days is the least duration that provides maximum efficacy for H. pylori in Egyptian participants. In addition, successful treatment of H. pylori infection may reduce the risk of anemia and dyslipidemia. Furthermore, all members of the patient's family should be screened for H. pylori to prevent recurrent infection.
Topics: Adolescent; Adult; Amoxicillin; Anti-Bacterial Agents; Dexlansoprazole; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Male; Middle Aged; Pilot Projects; Prospective Studies; Proton Pump Inhibitors; Time Factors; Treatment Outcome; Young Adult
PubMed: 33283766
DOI: 10.4103/ijp.IJP_364_19 -
Alimentary Pharmacology & Therapeutics May 2010Dexlansoprazole MR is a Dual Delayed Release proton pump inhibitor formulated to extend the duration of acid suppression. (Randomized Controlled Trial)
Randomized Controlled Trial
The effect of time-of-day dosing on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR: evidence for dosing flexibility with a Dual Delayed Release proton pump inhibitor.
BACKGROUND
Dexlansoprazole MR is a Dual Delayed Release proton pump inhibitor formulated to extend the duration of acid suppression.
AIM
To evaluate the pharmacokinetics and pharmacodynamics of dexlansoprazole MR dosed before 4 different meal times.
METHODS
In this randomized, open-label, four-way crossover study, 48 healthy subjects received dexlansoprazole MR 60 mg once daily 30 min before breakfast, lunch, dinner or an evening snack. Pharmacokinetics of dexlansoprazole MR and intragastric pH were assessed over a 24-h postdose interval on day 5 for each regimen.
RESULTS
Absorption was delayed when dexlansoprazole MR was administered before each regimen relative to breakfast; however, systemic exposures of dexlansoprazole at all regimens were bioequivalent. There were no statistically significant differences in mean 24-h intragastric pH between dosing before dinner or an evening snack vs. breakfast; however, there was a small (0.2), but statistically significant difference between lunch and breakfast. There was a statistically significant difference of 7 percentage points in the percentage of time intragastric pH was >4 for the snack regimen relative to the breakfast regimen, but there were no statistically significant differences between lunch or dinner compared with breakfast.
CONCLUSION
Dexlansoprazole MR provides comparable acid control when administered at different times of the day.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Anti-Ulcer Agents; Cross-Over Studies; Delayed-Action Preparations; Dexlansoprazole; Female; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Time Factors; Treatment Outcome; Young Adult
PubMed: 20180789
DOI: 10.1111/j.1365-2036.2010.04272.x -
Clinical and Translational Science Jan 2021There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic...
There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic children's hospital to determine the potential utility of PGx in diseases of childhood and to identify targets for future pediatric pharmacogenetic research. An actionable gene-drug pair associated with the 28 genes tested (Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B, Pharmacogenomics Knowledge Base (PharmGKB) level 1A or B, or US Food and Drug Administration (FDA) recommendation and a PharmGKB level) was present in 98.7% of patients. We identified 203 actionable gene-drug-diagnosis groups based on the indications for each actionable drug listed in Lexicomp. Among patients with an actionable gene-drug-diagnosis group, 49.3% had a diagnosis where the drug was a therapeutic option and PGx could be used to guide treatment selection. Among patients with an associated diagnosis, 30.9% had a prescription for the actionable drug allowing PGx guided dosing. Three genes (CYP2C19, CYP2D6, and CYP3A5) accounted for all the gene-drug-diagnosis groups with matching diagnoses and prescriptions. The most common gene-drug-diagnosis groups with matching diagnoses and prescriptions were CYP2C19-citalopram-escitalopram-depression 3.3% of patients tested; CYP2C19-dexlansoprazole-gastritis-esophagitis 3.1%; CYP2C19-omeprazole-gastritis-esophagitis 2.4%; CYP2D6-atomoxetine-attention deficit hyperactivity disorder 2.2%; and CYP2C19-citalopram-escitalopram-obsessive-compulsive disorder 1.5%. PGx could be used to guide selection of current treatment options or medication dosing in almost half (48.7%) of pediatric patients tested. Mood disorders and gastritis/esophagitis are promising targets for future study of PGx testing because of the high prevalence of these diagnoses and associated actionable gene-drug pairs in the pediatric population.
Topics: Academic Medical Centers; Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Clinical Decision-Making; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Depression; Dose-Response Relationship, Drug; Drug Prescriptions; Esophagitis; Feasibility Studies; Female; Gastritis; Hospitals, Pediatric; Humans; Male; Obsessive-Compulsive Disorder; Pharmacogenomic Testing; Pharmacogenomic Variants; Prescription Drugs; Retrospective Studies
PubMed: 33048453
DOI: 10.1111/cts.12895 -
Annals of Medicine Dec 2023Esophageal adenocarcinoma incidence has increased significantly despite surveillance endoscopy for Barrett's esophagus (BE) and gastric acid supression medications. This...
INTRODUCTION
Esophageal adenocarcinoma incidence has increased significantly despite surveillance endoscopy for Barrett's esophagus (BE) and gastric acid supression medications. This prospective, cohort study's aims were to determine the long-term efficacy of proton-pump inhibitors twice daily (PPI-BID) with cryotherapy (CRYO) for complete ablation of BE.
MATERIALS AND METHODS
Consecutive BE patients were managed with a PPI-BID, CRYO ablation, follow-up protocol. Primary outcomes were to determine complete ablation rate of intestinal metaplasia (IM) or dysplasia/carcinoma, and factors affecting recurrence.
RESULTS
Sixty-two patients were enrolled: advanced disease (11%), low-grade or indefinite dysplasia (26%), non-dysplastic BE (63%). In 58 completing CRYO, eradication was confirmed in 100% on surveillance endoscopy. Adverse events (5%) were minor (mild pain 4%). IM recurred in 9% after a mean of 52 months, all successfully re-ablated. No second recurrence occurred. The primary predictor of recurrence was noncompliance with PPI-BID. BE or cardia IM recurred in 35% of those taking proton pump inhibitors once daily or less compared with 0% in those on PPI-BID or dexlansoprazole daily (<.001).
CONCLUSIONS
Minimizing acid reflux with at least PPI-BID combined with CRYO ablation appears to be the optimal cost-effective and safe BE treatment for any stage to minimize progression to adenocarcinoma by addressing both the stimulus that causes BE and the presence of goblet cells.
Topics: Humans; Barrett Esophagus; Proton Pump Inhibitors; Cryosurgery; Cohort Studies; Prospective Studies; Adenocarcinoma
PubMed: 37232568
DOI: 10.1080/07853890.2023.2191002 -
Alimentary Pharmacology & Therapeutics Nov 2009Dexlansoprazole MR is a dual delayed release formulation of dexlansoprazole, an enantiomer of lansoprazole.
BACKGROUND
Dexlansoprazole MR is a dual delayed release formulation of dexlansoprazole, an enantiomer of lansoprazole.
AIM
To assess safety of dexlansoprazole MR in phase 3 clinical trials.
METHODS
Data from 4270 patients receiving dexlansoprazole MR 30 mg (n = 455), 60 mg (n = 2311) or 90 mg (n = 1864); lansoprazole 30 mg (n = 1363); or placebo (n = 896) in six randomized controlled trials and a 12-month safety study were pooled. Safety was assessed via adverse events, vital signs, electrocardiograms, clinical laboratory results and gastric biopsies. Adverse events were summarized per 100 patient-months of exposure to account for imbalances in study drug exposure.
RESULTS
The number of patients with > or =1 treatment-emergent adverse event per 100 patient-months was higher in placebo (24.49) and lansoprazole (21.06) groups than in any dexlansoprazole MR (15.64-18.75) group. Fewer patients receiving dexlansoprazole MR discontinued therapy because of an adverse event (P < or = 0.05 vs. placebo). Seven patients died of events considered unrelated to study drug. Mean serum gastrin rose in all groups except placebo; increases were not dose-related. No clinically concerning trends were seen in gastric biopsy results. Endocrine cell hyperplasia, dysplasia and neoplasia were not observed.
CONCLUSION
Dexlansoprazole MR 30-90 mg has a safety profile comparable to that of lansoprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Clinical Trials as Topic; Delayed-Action Preparations; Dexlansoprazole; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome
PubMed: 19735233
DOI: 10.1111/j.1365-2036.2009.04137.x -
Therapeutic Advances in Gastroenterology 2019Dexlansoprazole has been shown to be efficacious for the treatment of gastroesophageal reflux disease. However, there is a paucity of data about its efficacy for...
BACKGROUND
Dexlansoprazole has been shown to be efficacious for the treatment of gastroesophageal reflux disease. However, there is a paucity of data about its efficacy for eradication. The aim of this study was to evaluate the efficacy of dexlansoprazole for eradication as triple therapy in real-world practice.
METHODS
Adult patients with endoscopically proven related peptic ulcer diseases or gastritis were recruited for this study. The eradication status was assessed based on the results of the C-urea breath test performed 4 weeks after treatment. According to the different treatment regimens, the patients were allocated to group A: Esomeprazole 40 mg b.i.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d. for 7 days; group B: Esomeprazole 40 mg q.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d. for 7 days, or group C: Dexlansoprazole 60 mg q.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d. for 7 days.
RESULTS
A total of 215 patients (49% males) were enrolled in this study, with a mean age of 55 years. The eradication rates in group A, B, and C were 94.7% (71/75), 89.6% (69/77), and 93.7% (59/63) ( = 0.457), respectively. The adverse events were similar between the three groups ( = 0.068).
CONCLUSIONS
This study suggests that dexlansoprazole-based triple therapy has an acceptable eradication rate for infection.
PubMed: 31523277
DOI: 10.1177/1756284819870960 -
PloS One 2014Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully clarified through comparative studies. We aimed to evaluate the association between the use of PPI and the risk of developing hypomagnesemia by conducting a systematic review with meta-analysis.
METHODS
We conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "proton pump," "dexlansoprazole," "esomeprazole," "ilaprazole," "lansoprazole," "omeprazole," "pantoprazole," "rabeprazole," "hypomagnesemia," "hypomagnesaemia," and "magnesium." Studies were included if they evaluated the association between PPI use and hypomagnesemia and reported relative risks or odds ratios or provided data for their estimation. Pooled odds ratios with 95% confidence intervals were calculated using the random effects model. Statistical heterogeneity was assessed with Cochran's Q test and I2 statistics.
RESULTS
Nine studies including 115,455 patients were analyzed. The median Newcastle-Ottawa quality score for the included studies was seven (range, 6-9). Among patients taking PPIs, the median proportion of patients with hypomagnesemia was 27.1% (range, 11.3-55.2%) across all included studies. Among patients not taking PPIs, the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3-52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775 (95% confidence interval 1.077-2.924). Significant heterogeneity was identified using Cochran's Q test (df = 7, P<0.001, I2 = 98.0%).
CONCLUSIONS
PPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Magnesium; Odds Ratio; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Risk Factors; Treatment Outcome
PubMed: 25394217
DOI: 10.1371/journal.pone.0112558 -
Digestive Diseases and Sciences Mar 2018Approximately, 20% of patients with heartburn and normal endoscopic findings do not symptomatically improve on proton pump inhibitor (PPI) therapy making diagnosis and...
BACKGROUND
Approximately, 20% of patients with heartburn and normal endoscopic findings do not symptomatically improve on proton pump inhibitor (PPI) therapy making diagnosis and treatment uncertain. A biomarker distinguishing PPI-responsive from PPI-refractory heartburn is desirable.
AIMS
We performed a pilot study assessing whether carboxy(C)-terminal fragments (CTFs) of e-cadherin in esophageal biopsies or amino(N)-terminal fragments (NTFs) of e-cadherin in serum could serve this purpose.
METHODS
Twenty-nine patients with endoscopy-negative heartburn had esophageal biopsies for CTFs on Western blot and blood for serum NTFs on ELISA. All patients received dexlansoprazole 30 mg daily for 4 weeks, and heartburn was assessed by daily diary entry. Post-treatment blood samples were obtained for serum NTFs. A control group without GERD symptoms (n = 6) had biopsies for CTFs and a second control group (n = 20) blood serum for serum NTFs.
RESULTS
Twenty-seven of 29 patients (93.1%) with endoscopy-negative heartburn, but 0 of 6 controls, were positive for CTFs. All patients and controls had measureable serum NTFs, but mean NTFs were significantly higher in those with PPI-responsive heartburn compared to those with PPI-refractory heartburn and controls. Following treatment, 24 of 29 (82.8) patients had relief of heartburn, which associated with a decline in mean NTFs compared to controls. NTFs in PPI-refractory patients (n = 5) were similar to controls before and after PPI therapy.
CONCLUSIONS
When heartburn responds to PPI, elevated serum NTFs decline to normal. These data suggest that cleaved products of e-cadherin may serve as biomarkers of NERD. Further data are needed to assess and confirm this concept.
Topics: Adult; Antigens, CD; Biomarkers; Cadherins; Case-Control Studies; Dexlansoprazole; Esophagus; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Pilot Projects; Proton Pump Inhibitors
PubMed: 29071486
DOI: 10.1007/s10620-017-4815-4