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International Journal of Molecular... Sep 2022Proton 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+... (Review)
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.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Antacids; Bone Density; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Omeprazole; Osteoporotic Fractures; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; United States
PubMed: 36142643
DOI: 10.3390/ijms231810733 -
World Journal of Gastroenterology Oct 2012In the present paper the increasing difficulty of diagnosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues... (Review)
Review
In the present paper the increasing difficulty of diagnosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the perspective of clinical management.
Topics: Contraindications; Gastrins; Humans; Proton Pump Inhibitors; Zollinger-Ellison Syndrome
PubMed: 23112541
DOI: 10.3748/wjg.v18.i39.5495 -
Frontiers in Pharmacology 2022Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use... (Review)
Review
Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use in pediatrics is approved for children older than 1 year, for the short-term treatment of symptomatic gastroesophageal reflux disease (GERD), healing of erosive esophagitis, treatment of peptic ulcer disease, and eradication of . PPIs are also considered the standard of care for pediatric eosinophilic esophagitis. Despite the strict range of indications, the use of this class of molecules has increased in all pediatric age ranges. The long-term gastric acid suppression in children has been linked to increased risks of gastrointestinal and lower respiratory tract infections, bone fractures, and allergy. This study aims to provide a comprehensive overview of the mechanism of actions, use (and misuse) in infants and children, and safety of PPIs.
PubMed: 35222047
DOI: 10.3389/fphar.2022.839972 -
BMC Pharmacology & Toxicology Jul 2020The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole, rabeprazole, and pantoprazole.
SETTING
The study population comprised 186 healthy volunteers participating in 6 bioequivalence clinical trials.
METHOD
Subjects were evaluated to determine the effect of a high-fat breakfast on the pharmacokinetics of omeprazole (n = 36), rabeprazole (n = 69), and pantoprazole (n = 81).
MAIN OUTCOME MEASURE
Drug plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry.
RESULTS
Food affected the pharmacokinetics of omeprazole (increased T and decreased AUC and C), pantoprazole (increased T and decreased AUC), and rabeprazole (increased T, C and half-life). Food increased variability in T for all 3 drugs, delaying absorption around 3 to 4 h and until 20 h in some subjects.
CONCLUSION
As food delays the absorption of PPIs and increases their variability, it would be better to administer these drugs under fasting conditions.
TRIAL REGISTRATION
European Union Drug Regulating Authorities Clinical Trials Database: EudraCT : 2004-003863-59 (registration date 05/MAR/2004), EudraCT 2006-001162-17 (registration date 17-MAR-2006), EudraCT: 2007-002489-37 (registration date 12-JUN-2007), EudraCT: 2007-002490-31 (registration date 12-JUN-2007), EudraCT: 2010-024029-19 (registration date 23-NOV-2010).
Topics: Adult; Anti-Ulcer Agents; Cross-Over Studies; Cytochrome P-450 CYP2C19; Dietary Fats; Fasting; Female; Food-Drug Interactions; Genotype; Humans; Male; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Young Adult
PubMed: 32711578
DOI: 10.1186/s40360-020-00433-2 -
Clinical Gastroenterology and... Jun 2018Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials... (Comparative Study)
Comparative Study
Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials that performed pH testing in patients receiving solid-dose PPI formulations (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) for a minimum of 5 days. We used omeprazole equivalency and the surrogate biomarker, percentage time pH > 4 over a 24-hour period (pH4time), to compare PPI effectiveness for different PPIs given once, twice, or 3 times daily. We found that increasing strength of once-daily PPIs (9-64 mg omeprazole equivalents) increased pH4time linearly from approximately 10.0 to 15.6 hours; higher doses produced no further increase in pH4time. Increasing the frequency to twice-daily PPI increased pH4time linearly, from approximately 15.8 to 21.0 hours. Three-times daily PPIs performed similarly to twice-daily PPIs. The costs of PPIs varied greatly, but the cost variation was not directly related to potency. We conclude that PPIs can be used interchangeably based on potency. Using twice-daily PPIs is more effective in increasing efficacy increasing once-daily PPI dosage. Omeprazole and lansoprazole (30 mg) and 20 mg of esomeprazole rabeprazole are functionally equivalent.
Topics: Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28964908
DOI: 10.1016/j.cgh.2017.09.033 -
The Turkish Journal of Gastroenterology... Sep 2016Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastrıc pH in extensive metabolizer patients with gastroesophageal reflux disease.
BACKGROUND/AIMS
Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of these studies, comparison of only two PPIs have been made. There are few studies on the comparison of four or more PPIs. We aimed to compare the acid inhibitory effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on days 1 and 5 of treatment in patients with GERD, who were extensive metabolizers in regard to the CYP2C19 genotype.
MATERIALS AND METHODS
Helicobacter pylori-negative with typical symptoms of GERD patients were randomly divided into four treatment groups. Efficacy analysis on days 1 and 5 were performed on the four groups which comprised 10 (esomeprazole), 11 (rabeprazole), 10 (lansoprazole), and 10 (pantoprazole) patients.
RESULTS
On day 1 of PPI treatment, the mean percentage of time with intragastric Ph>4 were 54%, 58%, 60%, and 35% for the groups, respectively, and on day 5, these values were 67%, 60%, 68%, and 59%, respectively. Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment.
CONCLUSION
Pantoprazole is a less potent proton pump inhibitor than the other PPIs tested on the first day of treatment. When the time needed to raise the intragatric pH to over 4 was evaluated, esomeprazole was found to have the most rapid action, followed by lansoprazole and rabeprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Cross-Over Studies; Cytochrome P-450 CYP2C19; Double-Blind Method; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Genotype; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome
PubMed: 27782887
DOI: 10.5152/tjg.2016.15514 -
Alimentary Pharmacology & Therapeutics Sep 2015Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. Vonoprazan is a member of a new class of acid suppressants;... (Comparative Study)
Comparative Study Randomized Controlled Trial
Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects--a randomised open-label cross-over study.
BACKGROUND
Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. Vonoprazan is a member of a new class of acid suppressants; potassium-competitive acid blockers. Vonoprazan may thus be an alternative to PPIs.
AIM
To evaluate efficacy, rapidity and duration of acid-inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive metaboliser genotype.
METHODS
In this randomised, open-label, two-period cross-over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days. Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage of time pH ≥3, ≥4 and ≥5 (pH holding time ratios; HTRs) and mean gastric pH.
RESULTS
Acid-inhibitory effect (pH4 HTR) of vonoprazan was significantly greater than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% [95% confidence interval (CI): 16.2-33.1] and for vonoprazan vs. rabeprazole 28.8% [95% CI: 17.2-40.4]. The Day 1 to Day 7 ratio of 24-h pH4 HTRs was >0.8 for vonoprazan, compared with 0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well tolerated. One vonoprazan subject withdrew due to a rash which resolved after discontinuation.
CONCLUSIONS
This study demonstrated a more rapid and sustained acid-inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole 10 mg. Therefore, vonoprazan may be a potentially new treatment for acid-related diseases.
Topics: Adult; Cross-Over Studies; Esomeprazole; Gastric Acid; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Rabeprazole; Research Design; Sulfonamides
PubMed: 26193978
DOI: 10.1111/apt.13325 -
Chinese Medical Journal Dec 2022The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori ) infection status and CYP2C19 polymorphism on anaprazole.
METHODS
In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint.
RESULTS
The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%).
CONCLUSIONS
The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.
REGISTRATION
ClinicalTrials.gov, NCT04215653.
Topics: Humans; Rabeprazole; Duodenal Ulcer; Cytochrome P-450 CYP2C19; Omeprazole; Anti-Ulcer Agents; Amoxicillin; Proton Pump Inhibitors; Helicobacter Infections; Helicobacter pylori; Drug Therapy, Combination
PubMed: 36580650
DOI: 10.1097/CM9.0000000000002508