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Helicobacter Oct 2022The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection.
MATERIALS AND METHODS
The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared.
RESULTS
Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar.
CONCLUSIONS
Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.
Topics: Amoxicillin; Anti-Bacterial Agents; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Humans; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome
PubMed: 35939559
DOI: 10.1111/hel.12922 -
British Journal of Clinical Pharmacology Jan 2023We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. (Randomized Controlled Trial)
Randomized Controlled Trial
High-dose amoxicillin-proton pump inhibitor dual therapy as first-line treatment for Helicobacter pylori infection in Northwest China: A prospective, randomised controlled trial.
AIMS
We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China.
METHODS
A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by C urea breath test ( C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method.
RESULTS
The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured.
CONCLUSION
The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.
Topics: Humans; Helicobacter Infections; Amoxicillin; Helicobacter pylori; Proton Pump Inhibitors; Clarithromycin; Esomeprazole; Bismuth; Prospective Studies; Drug Therapy, Combination; Anti-Bacterial Agents; China; Treatment Outcome
PubMed: 35947524
DOI: 10.1111/bcp.15488 -
Alimentary Pharmacology & Therapeutics Oct 2004As the relative efficacy of therapeutic agents in the treatment of gastro-oesophageal reflux disease is related to how consistently and completely gastric acid secretion... (Review)
Review
As the relative efficacy of therapeutic agents in the treatment of gastro-oesophageal reflux disease is related to how consistently and completely gastric acid secretion is suppressed, intragastric pH monitoring is a useful tool in stratifying therapies. If there is no acid in the stomach, there can be none to reflux into the oesophagus. Comparative crossover studies have shown consistently that once-daily esomeprazole (40 mg) provides more effective and longer lasting intragastric acid control than any other proton pump inhibitor currently available in healthy subjects and patients with gastro-oesophageal reflux disease. However, esomeprazole maintained intragastric pH > 4 for > or = 16 h in only about 55% of individuals tested. Thus, if more complete acid suppression is desirable, twice-daily proton pump inhibitor therapy may be advantageous. One such scenario is in patients with Barrett's metaplasia. Data from the ProGERD study suggest that, for each Los Angeles grade of oesophagitis, the healing rate for patients with Barrett's metaplasia is 10-30% less than that for non-Barrett's patients, being as low as 53% in patients with Los Angeles grade D oesophagitis. Also relevant to the Barrett's metaplasia population are studies on the oesophageal mucosa, which show that effective acid suppression favours differentiation and decreases epithelial cell proliferation. Both considerations argue for more intensive gastric acid inhibition than can be achieved with once-daily therapy, leading to experimentation with twice-daily proton pump inhibitor regimens. A randomized, double-blind, three-way crossover study compared esomeprazole 40 mg once daily with esomeprazole 20 mg and 40 mg twice daily and found that both twice-daily regimens were superior, maintaining intragastric pH > 4 for 73%[95% confidence interval (CI), 67-79%] and 80% (95% CI, 75-86%) of the day, respectively, compared with 59% (95% CI, 54-65%) of the day with esomeprazole 40 mg once daily, arguing that a twice-daily regimen may be the preferred strategy for patients with Barrett's metaplasia.
Topics: Anti-Ulcer Agents; Barrett Esophagus; Esomeprazole; Esophagus; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Metaplasia; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 15456470
DOI: 10.1111/j.1365-2036.2004.02135.x -
Alimentary Pharmacology & Therapeutics Oct 2000The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators.
BACKGROUND
The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid-related disease.
METHODS
1960 patients with endoscopy-confirmed reflux oesophagitis (RO) were randomized to once daily esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double-blind trial. The primary efficacy variable was the proportion of patients healed at week 8. Secondary variables included healing and heartburn resolution at week 4, time to first resolution and sustained resolution of heartburn, and per cent of heartburn-free days and nights. Safety and tolerability were also evaluated.
RESULTS
Significantly more patients were healed at week 8 with esomeprazole 40 mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life table estimates, ITT analysis (each P < 0.05). Esomeprazole 40 mg was also significantly more effective than omeprazole for healing at week 4 and for all secondary variables evaluating heartburn resolution. The most common adverse events in all treatment groups were headache, abdominal pain and diarrhoea.
CONCLUSION
Esomeprazole was more effective than omeprazole in healing and symptom resolution in GERD patients with reflux oesophagitis, and had a tolerability profile comparable to that of omeprazole.
Topics: Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Heartburn; Humans; Male; Middle Aged; Omeprazole
PubMed: 11012468
DOI: 10.1046/j.1365-2036.2000.00856.x -
BioMed Research International 2015Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped...
Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped density (TD), compressibility index (Carr's index), Hauser's ratio (H), and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr's index 17.5%, Hauser's ratio 1.2, and sieve analysis time 5 minutes). There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350-2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation.
Topics: Biological Availability; Chemistry, Pharmaceutical; Humans; Omeprazole; Silicon Dioxide; Solubility; Tablets, Enteric-Coated; Water
PubMed: 25699270
DOI: 10.1155/2015/307032 -
British Journal of Clinical Pharmacology Oct 2022Esomeprazole is a proton pump inhibitor being investigated for treatment of preeclampsia. Esomeprazole pharmacokinetics during pregnancy are unknown. We used data from...
Esomeprazole is a proton pump inhibitor being investigated for treatment of preeclampsia. Esomeprazole pharmacokinetics during pregnancy are unknown. We used data from 10 pregnant participants with preterm preeclampsia, and 49 non-pregnant participants to develop a population pharmacokinetic model of esomeprazole. A two-compartment model described the data well. In pregnant participants after single dose, clearance was 42.2% (14.9-61.6%) lower compared to non-pregnant, most likely due to inhibition of CYP2C19. In non-pregnant participants after repeated dosing, clearance was 54.9% (48.2-63.5%) lower in extensive metabolizers and bioavailability was 33% (10.0-52.0%) higher compared to single dosing, which could be due to autoinhibition of CYP2C19. During pregnancy, the CYP2C19 autoinhibition effect with repeated dosing is expected to lead to much lower increase in exposure compared to non-pregnant individuals, since CYP2C19 is already inhibited due to pregnancy.
Topics: Cytochrome P-450 CYP2C19; Esomeprazole; Female; Humans; Infant, Newborn; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors
PubMed: 35599445
DOI: 10.1111/bcp.15416 -
Actas Dermo-sifiliograficas Oct 2011
Review
Topics: Aged; Anti-Inflammatory Agents; Anti-Ulcer Agents; Antibodies, Antinuclear; Biopsy; Comorbidity; Esomeprazole; Female; Humans; Lupus Erythematosus, Cutaneous; Mometasone Furoate; Polypharmacy; Pregnadienediols; Pruritus; Remission Induction; Thiamine; Vitamin B 12; Vitamin B 6
PubMed: 21641568
DOI: 10.1016/j.ad.2010.09.018 -
American Family Physician Jul 2002Since their introduction in the late 1980s, proton pump inhibitors have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers. Proton...
Since their introduction in the late 1980s, proton pump inhibitors have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers. Proton pump inhibitors have enabled improved treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal antiinflammatory drug-induced gastropathy. Proton pump inhibitors have minimal side effects and few significant drug interactions, and they are generally considered safe for long-term treatment. The proton pump inhibitors omeprazole, lansoprazole, rabeprazole, and the recently approved esomeprazole appear to have similar efficacy.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Benzimidazoles; Drug Interactions; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Omeprazole; Pantoprazole; Peptic Ulcer; Proton Pump Inhibitors; Rabeprazole; Sulfoxides
PubMed: 12152963
DOI: No ID Found -
British Journal of Clinical Pharmacology Feb 2000To determine the effect of grapefruit juice on omeprazole metabolism in vivo. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
AIMS
To determine the effect of grapefruit juice on omeprazole metabolism in vivo.
METHODS
This was a randomized crossover study with a 2 week washout period. Omeprazole (20 mg) was taken orally by 13 healthy volunteers after an overnight fast with either grapefruit juice or water. Serial blood samples were obtained over 12 h and standardized meals were served 3 and 10 h after the administration of omeprazole. Plasma concentrations of omeprazole and its major metabolites, 5-hydroxyomeprazole and omeprazole sulphone, were determined by high performance liquid chromatography (h.p.l.c.).
RESULTS
Mean area under the plasma concentration vs time curve (AUC) between 0 and 12 h for omeprazole sulphone was approximately 20% lower (P<0.01) in the group receiving grapefruit juice. There was no significant difference in the mean AUC of 5-hydroxyomeprazole or omeprazole. The AUC ratio of omeprazole sulphone to omeprazole, an index of CYP3A4 activity, was decreased by 33% (P<0.001) after administration of grapefruit juice whereas the AUC ratio of 5-hydroxyomeprazole to omeprazole, an index of CYP2C19 activity, did not differ between the two phases of the study. Although the time to peak concentration (tmax ) and terminal half-life (t1/2,z) of omeprazole and its two main metabolites were not altered, the peak concentration (Cmax ) of omeprazole sulphone was significantly reduced after administration of grapefruit juice.
CONCLUSION
Administration of grapefruit juice decreased the formation of omeprazole sulphone but not 5-hydroxyomeprazole. These results indicate that activities of CYP3A4, but not of CYP2C19, are inhibited by the simultaneous administration of grapefruit juice.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Beverages; Citrus; Cross-Over Studies; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Female; Humans; Male; Mixed Function Oxygenases; Omeprazole; Time Factors
PubMed: 10671908
DOI: 10.1046/j.1365-2125.2000.00122.x -
Drug Design, Development and Therapy 2015HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparison of the pharmacokinetics and tolerability of HCP1004 (a fixed-dose combination of naproxen and esomeprazole strontium) and VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium) in healthy volunteers.
BACKGROUND
HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO(®) (a marketed fixed-dose combination of naproxen and esomeprazole magnesium).
SUBJECTS AND METHODS
An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO(®)) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration-time curve from 0 to the last measurable time (AUC0-t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study.
RESULTS
Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation) and AUC0-t (mean ± standard deviation) for naproxen in HCP1004 were 61.67 ± 15.16 µg/mL and 1,206.52 ± 166.46 h · µg/mL, respectively; in VIMOVO(®); these values were 61.85 ± 14.54 µg/mL and 1,211.44 ± 170.01 h · µg/mL, respectively. The Cmax and AUC0-t for esomeprazole in HCP1004 were 658.21 ± 510.91 ng/mL and 1,109.11 ± 1,111.59 h · ng/mL, respectively; for VIMOVO(®), these values were 595.09 ± 364.23 ng/mL and 1,015.12 ± 952.98 h · ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO(®)) of the Cmax and AUC0-t of naproxen were 0.99 (0.94-1.06) and 1.00 (0.98-1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0-t were 0.99 (0.82-1.18) and 1.04 (0.91-1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either treatment.
CONCLUSION
The PK of HCP1004 500/20 mg was comparable to that of VIMOVO(®) 500/20 mg for both naproxen and esomeprazole after a single oral dose. Both drugs were well-tolerated without any safety issues.
Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Chemistry, Pharmaceutical; Cross-Over Studies; Drug Combinations; Esomeprazole; Half-Life; Healthy Volunteers; Humans; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Naproxen; Proton Pump Inhibitors; Republic of Korea; Young Adult
PubMed: 26257511
DOI: 10.2147/DDDT.S86725