The Effect of Dexlansoprazole on Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.

Proton Pump Inhibitors and Bone Health: An Update Narrative Review.

Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.

A Baeyer-Villiger monooxygenase from Cupriavidus basilensis catalyzes asymmetric synthesis of (R)-lansoprazole and other pharmaco-sulfoxides.

Biocatalytic synthesis of pharmaco-chiral sulfoxides has gained interest in recent years for its environmental friendliness. However, only a few natural biocatalysts can be used for the efficient synthesis of pharmaco-sulfoxides, including (R)-lansoprazole, a chiral proton pump inhibitor used to treat gastrointestinal diseases. In this study, the sequence of BoBVMO (Baeyer-Villiger monooxygenase from Bradyrhizobium oligotrophicum) was used as a probe to identify BVMOs via genomic mining for the highly efficient synthesis of (R)-lansoprazole and other pharmaco-sulfoxides. After virtual sequence filtering, target gene cloning, heterologous expression, and activity screening for lansoprazole sulfide (LPS) monooxygenation, seven new BVMOs were identified among more than 10,000 homologous BVMOs. According to the conserved sequence and phylogenetic tree analysis, these discovered enzymes belong to the family of type I BVMOs and the ethionamide monooxygenase subtype. Among them, CbBVMO, Baeyer-Villiger monooxygenase from Cupriavidus basilensis, showed the highest efficiency and excellent enantioselectivity for converting LPS into (R)-lansoprazole. Moreover, CbBVMO showed a wide substrate spectrum toward other bulky prazole-family sulfides. The results indicate that CbBVMO is a potential enzyme for extending the application of BVMOs in pharmaceutical industry. KEY POINTS: • CbBVMO is the most efficient biocatalyst for (R)-lansoprazole biosynthesis. • CbBVMO catalyzes the conversion of various bulky prazole sulfides. • CbBVMO is a promising enzyme for the biosynthesis of pharmaco-sulfoxides.

New spectroscopic methods for determination of dexlansoprazole using mercurochrome.

New spectroscopic methods were developed for dexlansoprazole estimation in capsule formulation based on the formation of a reaction between dexlansoprazole and Mercurochrome (MER) at pH 3.7. The formed complex was measured spectrophotometrically (Method I) at 557 nm and spectrofluorometrically (Method II) at 300 nm/538 nm, because the drug caused quantitative quenching of the native fluorescence of Mercurochrome. The spectrophotometric method was linear over the concentration 25-55 µg/ml with a limit of detection (LOD) of 1.15 µg/ml and a limit of quantification (LOQ) of 3.48 µg/ml. The spectrofluorometric method had a linear range 20-45 µg/ml with an LOD of 1.13 µg/ml and an LOQ of 3.45 µg/ml. The suggested methods were used to analyze capsules to test the interference from excipients and the data indicated good selectivity. Data obtained were statistically analyzed and were favourably good. The new methods are environmentally benign and depend on distilled water mainly as the diluting solvent. This property was confirmed by assessing their greenness.

Dexlansoprazole and Esomeprazole Do Not Affect Bone Homeostasis in Healthy Postmenopausal Women.

BACKGROUND & AIMS: Epidemiological studies have associated proton pump inhibitor (PPI) therapy with osteoporotic fractures, but it is not clear if PPIs directly cause osteoporosis. We evaluated the effect of dexlansoprazole and esomeprazole on bone turnover, bone mineral density (BMD), true fractional calcium absorption (TFCA), serum and urine levels of minerals, and levels of parathyroid hormone (PTH) in healthy postmenopausal women. METHODS: We performed a prospective, multicenter, double-blind study of 115 healthy, postmenopausal women (45 to 75 years of age) from November 4, 2010, through August 7, 2014. Women were randomly assigned to groups given dexlansoprazole (60 mg), esomeprazole (40 mg), or placebo daily for 26 weeks. We measured plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at 0 (baseline), 13, and 26 weeks. Primary outcomes were percent change in P1NP and CTX between weeks 0 and 26. We also measured changes in serum and urine levels of mineral, BMD, PTH (all subjects), and TFCA (n = 30). RESULTS: Between baseline and week 26, there were no significant within-group differences in markers of bone turnover; there was a nonsignificant increase in CTX levels in the dexlansoprazole group (0.12 ng/mL). The esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with the placebo group, although these values remained within normal ranges. There were no statistically significant differences between groups in serum or urine levels of minerals, BMD, or PTH at week 26. PPI therapy did not reduce TFCA. CONCLUSIONS: In a prospective study of postmenopausal women, we found significant increases in markers of bone turnover in women given PPI therapy compared with women given placebo, but levels remained within the normal reference range. We found no significant differences among groups in changes in BMD, PTH, serum or urine levels of minerals, or TFCA. Our findings indicate that 26 weeks of treatment with a PPI has no clinically meaningful effects on bone homeostasis. Clinicaltrials.gov no: NCT01216293.

Equivalent efficacies of reverse hybrid and concomitant therapies in first-line treatment of Helicobacter pylori infection.

BACKGROUND AND AIM: Concomitant therapy is a recommended first-line treatment for Helicobacter pylori infection in most national or international consensuses. Reverse hybrid therapy is a modified 14-day concomitant therapy without clarithromycin and metronidazole in the final 7 days. This study aims to test whether 14-day reverse hybrid therapy is non-inferior to 14-day concomitant therapy in the first-line treatment of H. pylori infection. METHODS: Helicobacter pylori-infected adult patients were randomly assigned to receive either reverse hybrid therapy (dexlansoprazole 60 mg o.d. plus amoxicillin 1 g b.d. for 14 days, and clarithromycin 500 mg plus metronidazole 500 mg b.d. for initial 7 days) or concomitant therapy (dexlansoprazole 60 mg once o.d. plus amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg b.d. for 14 days). H. pylori status was assessed 6 weeks after the end of treatment. RESULTS: Helicobacter pylori-infected participants (n = 248) were randomized to receive either 14-day reverse hybrid therapy (n = 124) or 14-day concomitant therapy (n = 124). Intention-to-treat analysis demonstrated that the two therapies had comparable eradication rate (95.2% vs 93.5%; 95% confidence interval, -4.0% to 7.4%; P = 0.582). However, reverse hybrid therapy had a much lower frequency of adverse events than concomitant therapy (20.2% vs 38.7%, P = 0.001). The two therapies exhibited comparable drug adherence (93.5% vs 87.9%, P = 0.125). CONCLUSIONS: Fourteen-day reverse hybrid therapy and 14-day concomitant therapy are equivalent in efficacy for the first-line treatment of H. pylori infection. However, reverse hybrid therapy has fewer adverse events compared with concomitant therapy.

Comparison of the efficiency of two different proton pump inhibitor formula in treatment of patients with atypical gastroesophageal reflux disease: a prospective randomized study.

BACKGROUND AND AIM: The prospective, open-label, randomized study aims to compare the efficacy of lansoprazole, a fast orally disintegrating proton pump inhibitor (PPI), and dexlansoprazole, a dual delayed release PPI, in patients with atypical symptoms of gastroesophageal reflux disease (GERD). METHODS: Patients with atypical GERD symptoms with a total reflux symptom index score > 10 were eligible for enrollment. From February 2018 to December 2019, 232 subjects were randomly assigned (1:1 ratio) to receive oral lansoprazole, Takepron OD 30 mg, once daily before breakfast or oral dexlansoprazole, Dexilant 60 mg, once daily before breakfast for 8 weeks. The primary end-point is to compare the symptoms response rate after an 8-week PPI therapy between the two groups. RESULTS: There were 232 study subjects enrolling in this study. After the 8-week PPI therapy, dexlansoprazole-treated group had a significantly higher response rate than lansoprazole-treated group in cough (76.5% vs 38.0%) and globus (69.7% vs 30.8%) (P all < 0.05 by intention-to-treat). Multivariate logistic regression analysis showed that the use of dexlansoprazole, presence of dyslipidemia, and typical GERD symptoms (acid reflux and heartburn) were predictors for symptom response for cough; the use of dexlansoprazole and presence of erosive esophagitis were predictors for symptom response for globus (P all < 0.05). No predictor for therapy response to hoarseness was noted. CONCLUSIONS: There is a higher response rate for cough and globus symptoms in patients with atypical GERD after the 8-week PPI therapy with dexlansoprazole rather than lansoprazole.

Dexlansoprazole is Effective in Relieving Heartburn during the Fasting Month of Ramadan.

BACKGROUND AND AIMS: Proton pump inhibitors are effective at reducing heartburn. No studies have evaluated their efficacy in Ramadan. Dexlansoprazole has a unique active formulation independent of time-of-day dosing or food. The aim is to investigate the efficacy of dexlansoprazole 60 mg during Ramadan in patients with symptomatic heartburn. METHODS: Subjects recruited using poster, radio, and SMS advertisements completed a diary using a mobile-friendly application and received daily SMS reminders. Dexlansoprazole was started on day 8 for 3 weeks. No placebo arm was used in this trial. Primary endpoint was relief of heartburn expressed as mean 24-h free heartburn percentage (24FH%) per weekly period. RESULTS: A total of 32 patients were enrolled. During week 1, only 1 person (3.1%) was heartburn-free and mean 24FH% was 41.1 ± 24.8%. On dexlansoprazole, mean 24FH% rose to 63.4 ± 23.8 and 81.6 ± 24.5% in weeks 2 and 4, respectively (p < 0.001 for both). Median 24FH% increased from 35.7% in week 1 to 71.4 and 85.7% in weeks 2 and 4, respectively. Mean Gastroesophageal Reflux Disease Questionnaire (GERDQ) scores decreased from 10.0 ± 3.2 in week 1 to 6.53 ± 2.2 in week 2 (p < 0.001) and 5.87 ± 2.1 in week 4 (p < 0.001). Mean heartburn severity score decreased from 2.5 ± 1.0 to 1.7 ± 0.8 (p = 0.001). Early response was higher in patients with GERDQ scores ≥8 (p = 0.012). CONCLUSION: Dexlansoprazole is effective in the treatment of heartburn during Ramadan. Clinicaltrials.gov number: NCT03079050.

Dual Delayed-Release Dexlansoprazole for Healing and Maintenance of Healed Erosive Esophagitis: A Safety Study in Adolescents.

BACKGROUND: In gastroesophageal reflux disease (GERD), the frequency of heartburn symptoms and erosive esophagitis (EE) increases with age in children and adolescents. Proton pump inhibitor, dexlansoprazole, is approved for healing EE of all grades, maintenance of healed EE, relief of heartburn, and treatment of symptomatic non-erosive GERD in patients ≥ 12 years. AIM: To assess safety and efficacy of dexlansoprazole dual delayed-release capsule in healing of EE and maintenance of healed EE in adolescents. METHODS: A multicenter, phase 2, 36-week study was conducted in 62 adolescents (12-17 years) with endoscopically confirmed EE. Patients received dexlansoprazole 60 mg once daily (QD) during open-label healing phase. Those with confirmed healing at week 8 were randomized to dexlansoprazole 30 mg QD or placebo during 16-week, double-blind maintenance phase, with subsequent treatment-free follow-up of ≥ 12 weeks. Primary endpoints were treatment-emergent adverse events (TEAEs) in ≥ 5% of patients during treatment. Secondary endpoints included percentages of patients with healing of EE and with maintenance of healed EE. RESULTS: 88% of patients achieved EE healing, and 61.3% reported a TEAE [headache (12.9%), oropharyngeal pain (8.1%), diarrhea (6.5%), and nasopharyngitis (6.5%)]. During maintenance phase, healing was maintained in 82% and 58% of dexlansoprazole and placebo groups, respectively. 72.0% of dexlansoprazole-treated patients reported TEAEs, which included headache (24.0%), abdominal pain (12.0%), nasopharyngitis (12.0%), pharyngitis (12.0%), sinusitis (12.0%), bronchitis (8.0%), upper respiratory tract infection (8.0%), and insomnia (8.0%); 61.5% experienced a TEAE with placebo. CONCLUSIONS: Dexlansoprazole is safe and efficacious for healing EE and maintenance of healed EE in adolescents.

Qualimetric analysis of proton pump inhibitors in Ukraine.

OBJECTIVE: Introduction: On the pharmaceutical market of Ukraine, there are six international non-proprietary names of proton pump inhibitors (PPIs) - Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole, Esomeprazole, Dexlansoprazole, which differ in a number of pharmacokinetic and pharmacodynamic parameters, safety profile, range of dosage forms and their cost. The aim: To investigate the competitiveness of proton pump inhibitors registered in Ukraine by comparing the parameters of their quality properties using the method of qualimetric analysis. PATIENTS AND METHODS: Materials and methods: Qualimetric analysis is based on the deductive-axiomatic approach, which allows quantifying the qualitative properties of drugs and determining the degree of competitiveness of each of them in the pharmaceutical market of Ukraine. The qualitative properties of PPIs in terms of consumer are efficacy, safety, convenience of use and cost. The subject of the study was 133 trademarks of PPIs registered in Ukraine. RESULTS: Results: The highest qualimetric values were obtained by omeprazole (Kk = 0.73) and its S-isomer esomeprazole (Kk = 0.66). Pantoprazole was inferior to them to a certain extent (Kk = 0.64). Lansoprazole (Kk = 0.53), rabeprazole (Kk = 0.50) and dexlansoprazole (Kk = 0.44) had the lowest values of the quality indices. CONCLUSION: Conclusions: According to the results of the study of the PPIs' competitiveness for parameters characterizing efficacy, safety, convenience of use and cost, assessed by qualimetric analysis, it has been established that the most completely and qualitatively satisfying consumer's needs are omeprazole and its S-isomer, esomeprazole.

Fragments of e-Cadherin as Biomarkers of Non-erosive Reflux Disease.

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.

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel.

Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.

Safety, tolerability, pharmacokinetics and pharmacodynamics of dexlansoprazole injection in healthy Chinese subjects.

PURPOSE: This study was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of dexlansoprazole injection in healthy subjects. METHODS: Dexlansoprazole (20-90 mg) or lansoprazole (30 mg) was administrated intravenously to healthy male and female volunteers. All the subjects were sampled for pharmacokinetic (PK) analysis and 64 of them were monitored for 24-h intragastric pH prior to and after administration in the pharmacodynamic (PD) study. RESULTS: Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-τ) for dexlansoprazole injection was dose-proportional over the range of 20-90 mg following a single intravenous administration. Total clearance and half-life (t1/2) was independent of dose, and ranged from 4.69 L/h to 5.85 L/h and from 1.24 h to 2.17 h, respectively. A single dose of dexlansoprazole (30 mg) resulted in higher gastric pH compared to that of lansoprazole, evidenced by a mean 24-h gastric pH of 6.1 ± 1.2 (lansoprazole: 5.4 ± 1.1) and 24-h gastric pH > 6 post drug dose holding time of 64.2 ± 21.0% (lansoprazole: 49.5 ± 21.5%). CONCLUSION: Dexlansoprazole injection was safe and well tolerated for up to 5-day repeated intravenous administration dose of 30 mg. The recommended dosage for dexlansoprazole injection is 30 mg for an adequate gastric acid control.

Dexlansoprazole for Heartburn Relief in Adolescents with Symptomatic, Nonerosive Gastro-esophageal Reflux Disease.

BACKGROUND: Proton pump inhibitors are commonly used to treat gastro-esophageal reflux disease (GERD) and nonerosive GERD (NERD) in adolescents and adults. Despite the efficacy of available medications, many patients have persisting symptoms, indicating a need for more effective agents. AIMS: To assess the safety and efficacy of dexlansoprazole dual delayed-release capsules in adolescents for treatment of symptomatic NERD. METHODS: A phase 2, open-label, multicenter study was conducted in adolescents aged 12-17 years. After a 21-day screening period, adolescents with endoscopically confirmed NERD received a daily dose of 30-mg dexlansoprazole for 4 weeks. The primary endpoint was treatment-emergent adverse events (TEAEs) experienced by ≥5% of patients. The secondary endpoint was the percentage of days with neither daytime nor nighttime heartburn. Heartburn symptoms and severity were recorded daily in patient electronic diaries and independently assessed by the investigator, along with patient-reported quality of life, at the beginning and end of the study. RESULTS: Diarrhea and headache were the only TEAEs reported by ≥5% of patients. Dexlansoprazole-treated patients (N = 104) reported a median 47.3% of days with neither daytime nor nighttime heartburn. Symptoms such as epigastric pain, acid regurgitation, and heartburn improved in severity for 73-80% of patients. Pediatric Gastroesophageal Symptom and Quality of Life Questionnaire-Adolescents-Short Form symptom and impact subscale scores (scaled 1-5) each decreased by an average of 0.7 units at week 4. CONCLUSIONS: Use of 30-mg dexlansoprazole in adolescent NERD was generally well tolerated and had beneficial effects on improving heartburn symptoms and quality of life. TRIAL REGISTRATION: This study has the ClinicalTrials.gov identifier NCT01642602.

Randomized controlled trial comparing esophageal dilation to no dilation among adults with esophageal eosinophilia and dysphagia.

The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P < 0.001) but similar reduction in mean dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy.

High-dose extended-release lansoprazole (dexlansoprazole) and amoxicillin dual therapy for Helicobacter pylori infections.

BACKGROUND: Helicobacter pylori infections have become increasingly difficult to treat. AIM: To examine whether amoxicillin and high-dose dexlansoprazole would reliably achieve an H. pylori eradication rate of ≥90%. METHODS: An open-label prospective pilot study of H. pylori eradication in treatment-naïve subjects with active H. pylori infection (positive by two tests). THERAPY: amoxicillin 1 g and dexlansoprazole 120 mg each twice a day at approximately 12-hour intervals for 14 days. Success was accessed by urea breath test. An effective therapy was defined as a per-protocol treatment success of 90% or greater; treatment success of 80% or less was prespecified as an unacceptable result. RESULTS: After 13 subjects were entered (12 men, one woman; average age of 54 years), the prespecified stopping rule of six treatment failures was achieved (i.e., the 95% confidence interval excluded achieving the required 90% success rate even if the proposed study of 50 completed patients were entered) and enrollment was stopped. Per-protocol and intention-to-treat treatment success were both 53.8%; (7/13); 95% CI = 25-80%. Compliance was 100%. Three patients (23%) reported side effects, all of which were mild and none interrupted therapy. CONCLUSION: Theoretically, dual PPI plus amoxicillin should reliably eradicate H. pylori provided nearly neutral intragastric pH can be maintained. Clearly, dexlansoprazole, despite being administered at high dose and twice a day (i.e., total daily dose 240 mg), failed to achieve an intragastric milieu consistent with dual PPI plus amoxicillin therapy being an effective anti-H. pylori regimen.

Comparison of Pharmacodynamics between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study.

Background/Aims: Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects. Methods: In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation. Results: All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration-time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing. Conclusions: All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.

Comparison of acid-lowering drugs for endoscopy negative reflux disease: Systematic review and network Meta-Analysis.

BACKGROUND: The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease. METHODS: We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score. KEY RESULTS: We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10 mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated. CONCLUSIONS & INFERENCES: Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.