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Medicine Nov 2022Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE.
METHODS
Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment.
RESULTS
A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo.
CONCLUSIONS
Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.
Topics: Humans; Proton Pump Inhibitors; Esomeprazole; Network Meta-Analysis; Peptic Ulcer; Rabeprazole; Esophagitis, Peptic; Abdominal Injuries
PubMed: 36451489
DOI: 10.1097/MD.0000000000031807 -
Hypertension (Dallas, Tex. : 1979) Jun 2022Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors. (Randomized Controlled Trial)
Randomized Controlled Trial
Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).
BACKGROUND
Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors.
METHODS
Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT-proET-1 after 4 days of omeprazole versus 20 preeclamptic women not receiving omeprazole.
RESULTS
Mean maternal age was 30 years, and median gestational age was 30 weeks. Baseline sFlt-1 levels were identical in both groups, and the same was true for PlGF or CT-proET-1. After 4 days, sFlt-1 levels remained similar in women not receiving omeprazole compared with women receiving omeprazole, while the levels of PlGF and CT-proET-1 also did not differ between groups. Women receiving omeprazole had a similar prolongation of pregnancy after inclusion compared with those in the nonomeprazole group (median 15 versus 14 days). Except for a higher neonatal intubation rate in the nonomeprazole group (31% versus 4%, =0.02), there were no differences in maternal/perinatal complications. Finally, making use of the placenta perfusion model, we established that both omeprazole and its S-isomer, esomeprazole, when maternally applied, reached the fetal compartment (fetal-to-maternal ratio's 0.43-0.59), while only esomeprazole inhibited placental sFlt-1 release.
CONCLUSIONS
Administration of omeprazole to women with confirmed preeclampsia does not alter their circulating levels of sFlt-1, PlGF, or ET-1, arguing against a role of this drug as a treatment for this syndrome.
Topics: Adult; Biomarkers; Endothelin-1; Esomeprazole; Female; Humans; Infant; Infant, Newborn; Omeprazole; Placenta; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1
PubMed: 35341328
DOI: 10.1161/HYPERTENSIONAHA.122.19070 -
Alimentary Pharmacology & Therapeutics Oct 2001Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid-related diseases. (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid-related diseases.
AIM
To examine the pharmacokinetics and pharmacodynamics of esomeprazole.
METHODS
In a crossover study, 12 healthy males received 5, 10 or 20 mg of esomeprazole, or 20 mg of omeprazole, once daily over 5 days. The pharmacokinetics and effects on pentagastrin-stimulated peak acid output of esomeprazole and omeprazole were studied on days 1 and 5.
RESULTS
The area under the curve (AUC) of both esomeprazole and omeprazole increased from day 1 to day 5. The correlation between acid inhibition and AUC for esomeprazole could be well described with a sigmoid Emax model. The mean inhibition values of the pentagastrin-stimulated peak acid output on day 1 for 5, 10 and 20 mg of esomeprazole were 15%, 29% and 46%, respectively; the corresponding day 5 values were 28%, 62% and 90%. The mean inhibition values of the pentagastrin-stimulated peak acid output for omeprazole were 35% (day 1) to 79% (day 5).
CONCLUSIONS
The pharmacokinetics of esomeprazole are time and dose dependent. There was a good correlation between AUC and effect for esomeprazole. These data suggest an increased acid inhibitory effect of esomeprazole compared to omeprazole.
Topics: Administration, Oral; Adult; Anti-Ulcer Agents; Area Under Curve; Cross-Over Studies; Esomeprazole; Gastric Acid; Gastric Acidity Determination; Gastrointestinal Agents; Humans; Male; Omeprazole; Pentagastrin; Proton Pump Inhibitors; Proton Pumps; Stereoisomerism; Time Factors
PubMed: 11563995
DOI: 10.1046/j.1365-2036.2001.01087.x -
Drug Metabolism and Pharmacokinetics Jun 2005Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are mainly metabolized by CYP2C19 in the liver. There are... (Review)
Review
Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are mainly metabolized by CYP2C19 in the liver. There are genetically determined differences in the activity of this enzyme. The genotypes of CYP2C19 are classified into the three groups, rapid extensive metabolizer (RM), intermediate metabolizer (IM), and poor metabolizer (PM). The pharmacokinetics and pharmacodynamics of PPIs depend on CYP2C19 genotype status. Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest of the three groups. These CYP2C19 genotype-dependent differences in pharmacokinetics and pharmacodynamics of PPIs influence the cure rates for the gastro-esophageal reflux disease and H. pylori infection by PPI-based therapies. For the better PPI-based treatment, doses and dosing schemes of PPIs should be optimized based on CYP2C19 genotype status.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Clarithromycin; Cytochrome P-450 CYP2C19; Drug Interactions; Drug Therapy, Combination; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Mixed Function Oxygenases; Omeprazole; Polymorphism, Genetic; Proton Pump Inhibitors; Rabeprazole
PubMed: 15988117
DOI: 10.2133/dmpk.20.153 -
Clinical Interventions in Aging 2013Peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD) are not uncommon in elderly patients. Clinical presentations of these acid-related disorders may be... (Review)
Review
Peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD) are not uncommon in elderly patients. Clinical presentations of these acid-related disorders may be atypical in the geriatric population. Older individuals are at increased risk for poor outcomes in complicated PUD and for development of GERD complications. Multiple risk factors (eg, Helicobacter pylori [HP], use of nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin) contribute to the development of PUD. Recent data has shown that HP-negative, NSAID-negative idiopathic peptic ulcers are on the rise and carry a higher risk of recurrent ulcer bleeding and mortality. Effective management of PUD in the geriatric population relies on identification and modification of treatable risk factors. Elderly patients with GERD often require long-term acid suppressive therapy. Proton pump inhibitors (PPI) including esomeprazole are effective in the treatment of reflux esophagitis, maintenance of GERD symptomatic control, and management of PUD as well as its complications. Potential safety concerns of long-term PPI use have been reported in the literature. Clinicians should balance the risks and benefits before committing elderly patients to long-term PPI therapy.
Topics: Aged; Anti-Ulcer Agents; China; Esomeprazole; Female; Gastroesophageal Reflux; Hong Kong; Humans; Male; Peptic Ulcer
PubMed: 24187492
DOI: 10.2147/CIA.S41350 -
Alimentary Pharmacology & Therapeutics May 2001Single daily doses of proton pump inhibitors, omeprazole and lansoprazole provide effective acid suppression and equal healing and symptom relief in patients with GERD.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Single daily doses of proton pump inhibitors, omeprazole and lansoprazole provide effective acid suppression and equal healing and symptom relief in patients with GERD. Despite this, controversy exists as to the efficacy of available proton pump inhibitors in the control of gastric acidity.
AIM
To assess the efficacy of omeprazole 20 mg vs. lansoprazole 30 mg and omeprazole 40 mg vs. lansoprazole 30 mg in intragastric pH control.
METHODS
Study I: 12 Helicobacter pylori-negative volunteers (mean age 33 years) were treated with omeprazole 20 mg and lansoprazole 30 mg in random order before breakfast for 7 days. Study II: 24 subjects (mean age 36 years) were similarly treated with omeprazole 40 mg and lansoprazole 30 mg for 7 days after a baseline pH study. One week washout was allowed between studies. Subjects had the same meal on each study day. On day seven, a 24-h intragastric pH study was performed. The percentage time for which gastric pH > 4 was analysed (Gastrosoft, Synectics Medical Inc.) and expressed as mean +/- s.d.
RESULTS
(1) Omeprazole 20 mg and lansoprazole 30 mg showed no significant difference in the percentage time for which gastric pH > 4 in the daytime and night-time periods. (2) The percentage time for which pH > 4 with omeprazole 40 mg was significantly greater than lansoprazole 30 mg in both daytime (61 +/- 19% vs. 48 +/- 14%, P < 0.001), and night-time periods (34 +/- 21% vs. 26 +/- 14%, P < 0.05). (3) A large inter-subject variation existed in both studies. (4) In 10 subjects who participated in both studies, omeprazole 40 mg showed a significantly higher percentage time for which pH > 4 in the daytime (69 +/- 18% vs. 51 +/- 15%, P=0.015) than omeprazole 20 mg.
CONCLUSION
These pH data support the therapeutic equivalency of FDA approved doses of omeprazole and lansoprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Circadian Rhythm; Cross-Over Studies; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Therapeutic Equivalency
PubMed: 11328258
DOI: 10.1046/j.1365-2036.2001.00967.x -
Drug Design, Development and Therapy 2022YYD601 was developed as a novel dual delayed release (DDR) formulation of esomeprazole to prolong the plasma esomeprazole concentration and extend the duration of acid... (Randomized Controlled Trial)
Randomized Controlled Trial
Pharmacokinetics and Pharmacodynamics of YYD601, a Dual Delayed-Release Formulation of Esomeprazole, Following Single and Multiple Doses in Healthy Adult Volunteers Under Fasting and Fed Conditions.
BACKGROUND
YYD601 was developed as a novel dual delayed release (DDR) formulation of esomeprazole to prolong the plasma esomeprazole concentration and extend the duration of acid suppression.
PURPOSE
The pharmacokinetic (PK) and pharmacodynamics (PD) characteristics of YYD601 after single and multiple oral administrations were investigated in healthy Korean adults under fasting and fed conditions, and compared with the original esomeprazole capsule.
METHODS
In the single-center, randomized, open-label, parallel-design, two-period study, thirty two volunteers were enrolled into four dosing groups, including esomeprazole 40-mg (group A), YYD60130-mg (group B), YYD601 40-mg (group C), and YYD601 60-mg (group D) once daily for 5 days. Blood samples were collected for PK analysis, before and up to 24 h after dosing. For PD characteristics of YYD601, the percentages of time with intragastric pH > 4 over a 24-h period and during night-time following multiple oral administrations were evaluated.
RESULTS
A total of 27 subjects completed the study. YYD601 showed a dual-peak PK profile under fasting condition, with delayed T compared with conventional formulation. There were no significant differences in the AUC values adjusted for dose between the three YYD601 dosage groups and the conventional esomeprazole 40 mg. The esomeprazole AUC following single and multiple administration decreased with food intake by approximately 33%. YYD601 showed a linear pharmacokinetic profile in the dose range studied. There was no statistically significant difference in increase in mean percentage of time with intragastric pH > 4 for 24-hour and during night-time between the three different doses of YYD601 and the conventional formulation. The treatments were well-tolerated during the study and no serious adverse events were observed.
CONCLUSION
YYD601 30 mg has a comparable effect on gastric acid inhibition as conventional esomeprazole 40 mg following once daily oral administration. Single and multiple oral dosing of YYD601 up to 60 mg were safe and well-tolerated throughout the study.
CLINICAL TRIAL REGISTRY
http://clinicaltrials.gov, NCT03558477 (date of registration: June 15, 2018; study period: between October 2017 and February 2018).
Topics: Administration, Oral; Adult; Area Under Curve; Cross-Over Studies; Esomeprazole; Fasting; Healthy Volunteers; Humans; Volunteers
PubMed: 35281316
DOI: 10.2147/DDDT.S338131 -
Alimentary Pharmacology & Therapeutics Feb 2003Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor available for clinical use as a single isomer. It demonstrates pharmacological and clinical... (Review)
Review
Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor available for clinical use as a single isomer. It demonstrates pharmacological and clinical benefits beyond those seen with the racemic omeprazole. Esomeprazole has higher and more consistent bio-availability than omeprazole, which results in a greater area under the plasma concentration-time curve. It is the area under the plasma concentration-time curve of omeprazole and esomeprazole that determines how much of each reaches the parietal cell, and thus the control of gastric acid secretion that is achieved. Esomeprazole, like other proton pump inhibitors, has a high specificity for the acidic environment of the parietal cell, where it is accumulated, activated and covalently inhibits the proton pump. Proton pumps elsewhere in the body do not achieve the level of acidity needed for accumulation and activation. Esomeprazole, 40 mg once daily, provides more effective control of gastric acid secretion than omeprazole, 20 or 40 mg once daily, and all other proton pump inhibitors given at their standard doses. This translates into greater clinical effect compared with omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily, in the management of reflux disease. Esomeprazole therapy is well tolerated, with a low adverse events profile, similar to that seen with omeprazole.
Topics: Anti-Ulcer Agents; Biological Availability; Esomeprazole; Gastric Acid; Humans; Omeprazole; Proton Pump Inhibitors
PubMed: 12622756
DOI: 10.1046/j.1365-2036.2003.01481.x -
BMC Gastroenterology Dec 2023Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.
BACKGROUND
Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE).
METHODS
We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups.
RESULTS
By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups.
CONCLUSIONS
The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD.
TRIAL REGISTRATION
NCT04080726 ( https://classic.
CLINICALTRIALS
gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.
Topics: Humans; Double-Blind Method; Esomeprazole; Esophagitis; Esophagitis, Peptic; Gastroesophageal Reflux; Peptic Ulcer; Proton Pump Inhibitors; Treatment Outcome
PubMed: 38110901
DOI: 10.1186/s12876-023-03087-6 -
British Journal of Clinical Pharmacology May 19901. Ten healthy subjects were given 20 mg omeprazole EC (enteric coated) granules once daily for 8 days. An i.v. tracer dose of [14C]-omeprazole was given simultaneously...
1. Ten healthy subjects were given 20 mg omeprazole EC (enteric coated) granules once daily for 8 days. An i.v. tracer dose of [14C]-omeprazole was given simultaneously with the first and last oral doses and blood sampling was performed thereafter. In order to study the extent of absorption at minimal acid exposure, a single dose of 20 mg omeprazole was also given as a buffered solution, before and after the treatment with EC granules. 2. Kinetic parameters of omeprazole after the i.v. tracer dose were unchanged on repeated dosing while AUC increased by approximately 40% for the solution and 60% for the EC granules. 3. The increased AUC is caused by an increased systemic availability, which may be explained by a decreased first-pass elimination during repeated treatment and/or by a reduced degradation of omeprazole in the stomach secondary to the profound decrease in intragastric acidity caused by the drug. 4. The implication of these findings is that the antisecretory effect of therapeutic doses of omeprazole must be studied during repeated administration and not judged from studies using single doses only.
Topics: Adult; Biological Availability; Buffers; Half-Life; Humans; Male; Omeprazole; Powders; Solutions
PubMed: 2350532
DOI: 10.1111/j.1365-2125.1990.tb03679.x