Treatment Of Acid-related Disorders Research Articles

Spatial Variation of the Gastrointestinal Microbiota in Response to Long-Term Administration of Vonoprazan in Mice With High Risk of Gastric Cancer.

Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure. Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing. Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group. Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.

Рабепразол в лечении кислотозависимых заболеваний

Proton-pump inhibitors (PPIs) are widely used to treat acid-related disorders (ARD). Rabeprazole is a potent inhibitor of gastric H+/K+-ATPase, and it is indicated for the treatment of gastroesophageal reflux disease, Zollinger-Ellison syndrome, gastric and duodenal ulcers and for Helicobacter pylori eradication (in combination with antibiotics), as well as for the treatment of ARD described in this article. Pharmacokinetic and pharmacodynamic data show that rabeprazole provides a marked acid inhibition from the first administration, which persists with repeated use. Due to the predominantly non-enzymatic metabolism, rabeprazole has a lower interaction potential between drugs. Besides, rabeprazole maintains a high intragastric pH and achieves maximum acid inhibition in 24 hours. Rabeprazole is characterized by linearity of pharmacokinetics, which remains unchanged in renal and hepatic insufficiency. Rabeprazole is available in the dosage form of enteric capsules due to the PPIs instability in an acidic environment. Rabeprazole is generally well-tolerated by patients. Besides several minor side effects, rabeprazole is safe to be widely used in the treatment of ARD. KEYWORDS: proton pump inhibitors, antisecretory drugs, rabeprazole, efficacy, safety, expediency, acid-related disorders, gastroesophageal reflux disease, peptic ulcer, gastropathy, dyspepsia. FOR CITATION: Tsukanov V.V. Rabeprazole in the treatment of acid-related disorders. Russian Medical Inquiry. 2023;7(5):264–273 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-4.

Acid Suppressive Drugs

Histamine H2 receptor antagonists (H2RAs) suppress gastric acid production by blocking H2 receptors in parietal cells. Studies have shown that proton pump inhibitors (PPIs) are superior to H2RAs as a treatment for acid-related disorders, such as peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). PPIs reduce gastric acid production by irreversibly inhibiting the H+/K+ ATPase pump, and they also increase gastric emptying. Although PPIs have differing pharmacokinetic properties, each PPI is effective in managing GERD and PUDs. However, PPIs have some limitations, including short plasma half-lives, breakthrough symptoms (especially at night), meal-associated dosing, and concerns associated with long-term PPI use. Potassium-competitive acid blockers (P-CABs) provide more rapid and profound suppression of intragastric acidity than PPIs. P-CABs are non-inferior to lansoprazole in healing erosive esophagitis and peptic ulcers, and may also be effective in improving symptoms in patients with non-erosive reflux disease. Acid suppressive drugs are the most commonly used drugs in clinical practice, and it is necessary to understand the pharmacological properties and adverse effects of each drug.

An update of pharmacology, efficacy, and safety of vonoprazan in acid-related disorders

ABSTRACT Introduction Patients with acid-related disorders (ARDs) of the upper digestive tract remain highly prevalent and need to be continuously investigated to improve their management. Areas covered This review provides a summary of the most recent advancements in the treatment of ARDs with particular focus on the new drugs available to overcome the unmet needs of traditional therapies. Expert opinion Proton pump inhibitors remain the best therapy in treating ARDs, but a consistent proportion of these patients continues to present mucosal lesions or to experience symptoms despite treatment. These cases pertain mainly to the most severe forms of erosive esophagitis or to non-erosive reflux disease. Also, the increasing rate of patients with H. pylori infection not responding to eradication therapy represents a difficult clinical condition. The recent advent of a new class of antisecretory drugs, such as the potassium competitive acid blockers and, among them the most studied vonoprazan, which are characterized by a better pharmacological profile than PPIs (rapid onset of action, longer lasting acid suppression, control of nocturnal acidity), has the potential to overcome the above-mentioned unmet needs. More research should be done to assess their efficacy in Western populations and their safety in patients treated in the long term.

Место препаратов висмута в лечении кислотозависимых заболеваний у детей

The article deals with the current problems of the prevalence, diagnosis and treatment of acid-related disorders in children. The administrative and legal aspects of the state regulation of measures aimed at diagnosing Helicobacter pylori infection, procurement of drugs for its treatment in the Russian Federation are discussed. The article also focuses on the standards of treatment of H. pylori infection in children with regard to age restrictions for the administration of the recommended drugs. A detailed account of the mechanisms of the developing H. pylori resistance to modern antibacterial drugs is given. The above problems necessitate the use of highly effective and safe drugs with low H. pylori resistance and approved for administration in children. The article indicates the already established and hypothesised factors of the pathogen’s low resistance to bismuth preparations. The multifactor, predominantly local, pharmacodynamic effect of bismuth tripotassium dicitrate in children ≥ 4 years of age is described. Data on the clinical effectiveness and high safety of this compound in H. pylori eradication therapy in paediatric population are also presented. Key words: acid-related disorders, Helicobacter pylori, standards for diagnosis and treatment of H. pylori in children, antibiotic resistance, bismuth tripotassium dicitrat

Proton Pump Inhibitors: for What and for How Long

Proton pump inhibitors (PPIs) have been used for over 25 years and are valuable agents in treatment of acid-related disorders. Recently, literature has demonstrated an association of PPI use with various risks. The purpose of this comprehensive review is to summarize current evidence-based indications and treatment durations of PPIs. A PubMed literature search was performed to identify clinical studies evaluating efficacy and/or safety of PPI use for specific indications and relevant guidelines on PPI indications. As of 2019, the Food and Drug Administration of the USA has approved PPIs for the following: (1) gastrointestinal acid reflux disease, (2) peptic ulcer disease, (3) eradication of H. pylori, (4) non-steroidal anti-inflammatory drug-induced ulcers, and (5) Zollinger-Ellison syndrome. Non-FDA-approved indications with evidence of benefit include acute upper gastrointestinal bleeding, stress ulcer prophylaxis, short bowel syndrome, and allograft protection after lung transplant. PPIs are indicated for 4–8 weeks in the treatment of GERD, and peptic ulcer disease, 10–14 days in the treatment of H. pylori, up to 12 months in short bowel syndrome, and indefinitely in lung transplant.

Tegoprazan to treat gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder in the United States. Although proton pump inhibitors (PPIs) are the mainstay of therapy for GERD and its complications, they have several limitations, including incomplete symptom resolution. Potassium-competitive acid blockers (P-CABs) were developed to address the limitations of PPIs as well as the need for improved antisecretory effects. Tegoprazan, the newest P-CAB, was approved in 2018 in South Korea for the treatment of erosive esophagitis (EE) and nonerosive reflux disease (NERD). A highly selective inhibitor of the H+/K+-ATPase, tegoprazan is also safe and effective for nocturnal acid breakthrough (NAB) and motility. Further studies of tegoprazan are warranted to define its potential role in the treatment of acid-related disorders.

The Effect of H2 Receptor Antagonist in Acid Inhibition and Its Clinical Efficacy.

The first histamine H2 receptor antagonists (H2RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H2RAs block the production of acid by H+, K+-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H2RAs are highly selective, and they do not affect H1 receptors. Moreover, they are not anticholinergic agents. Sequential development of H2RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H2RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H2RAs at night. The effectiveness of nighttime dose of H2RA suggests a major role of histamine in nocturnal acid secretion. H2RAs reduce secretion of gastric acid, and each H2RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H2RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders.

IN VITRO AND IN VIVO EVALUATION OF THE GASTRORETENTIVE FLOATING DOSAGE FORM

The aim of the present investigation was to develop and optimize gastro retentive floating system of Pantoprazole f or the efficient treatment of acid related disorders and H. Pylori infections. Floating tablets were developed using central composite design (CCD), and optimization was done by employing resp onse surface methodology . The floating tablets were prepared wit h HPMC K 4 M/Ethyl cellulose and natural seed polymer of Delonix regia by wet granulation technique. Buoyancy was achieved by adding an effervescent mixture of sodium bicarbonate and anhydrous citric acid. The Optim ized formulation (BS 3 ) showed no significan t change in physical appearance, drug content, total buoyancy time, or in vitro dissolution pattern after storage at 40°C/75 % relative humidity for 1 month. The best formulation was selected based on in vitro characteristics and was used for the in vivo r adiographi c studies by incorporating BaSO 4 . Evaluation of Gastric retention using x - Ray imaging studies were performed on rabbit to justify the increased gastric residence time of the dosage form in the stomach, based on the floating principle. Further the floating tablets were evaluated for its antiulcer activity in Male wristar rats by ethanol induced ulcer in comparison with standard. The floating formulation shows excellent buoyancy and better gastric cytoprotection when compare d with standard drug.

A novel nanoparticulate system for sustained delivery of acid-labile lansoprazole

In the present study, an effort was made to develop the Eudragit RS100 based nanoparticulate system for sustained delivery of an acid-labile drug, lansoprazole (LPZ). LPZ-loaded Eudragit RS100 nanoparticles (ERSNPs) were prepared by oil-in-water emulsion-solvent evaporation method. The effects of various formulation variables such as polymer concentration, drug amount and solvent composition on physicochemical performance of nanoparticles and in vitro drug release were investigated. All nanoparticles were spherical with particle size 198.9±8.6–376.9±5.6nm and zeta potential +35.1±1.7 to +40.2±0.8mV. The yield of nanoparticles was unaffected by change of these three variables. However, the drug loading and encapsulation efficiency were affected by polymer concentration and drug amount. On the other hand, the particle size of nanoparticles was significantly affected by polymer concentration and internal phase composition due to influence of droplet size during emulsification process. All nanoparticles prolonged drug release for 24h which was dominated by a combination of drug diffusion and polymer chain relaxation. The fastest and the slowest release rates were observed in C2-1002-10/0 and C8-4001-10/0, respectively, based on the release rate constant (k). Thus, the developed nanoparticles possessed a potential as a nano-carrier to sustain drug delivery for treatment of acid related disorders.

Improvement in Photostability of Pantoprazole Sodium by Microencapsulation

Pantoprazole sodium is a proton pump inhibitor used to treat peptic ulcers and gastroesophageal reflux. This drug is unstable in acid solution, in the presence of salts, as well as in UVC radiation. Hence the aim of present study was to develop microparticles that will protect the drug from degradation in gastric acid and increase its photostability. Microparticles were prepared by the solvent evaporation method using Eudragit S 100 as enteric polymer by varying drug: polymer ratios ranging from 1:1 to 1:4. The developed microparticles were characterized for surface morphology, particle size, encapsulation efficiency, and stability in acidic media. Microparticles obtained with the ratio 1:4 were spherical, had a smooth surface, and showed the highest percent entrapment of 67 ± 2.1%. Microparticles showed uniform size distribution; about 87% of microparticles were in the size range of 50 to 75 μm. In vitro dissolution studies showed no drug release in acidic media; further prolonged drug release for a period of 9 h was obtained with a 1:4 in phosphate buffer pH 7.4 following Higuchi release kinetics with regression value of 0.9896. Photodegradation studies were performed in solar light and in UV light at 254 nm and 366 nm for 7 days. The concentration of drug was determined spectrophotometrically at 290 nm. Percent degradation under solar light for pure drug was 25%, and no significant degradation was seen in drug-loaded microparticles. Degradation under UV radiation 254 nm and 366 nm was found to be 38.6% and 12.11% and 35.11% and 6.13% for pure drug and drug-loaded microparticles respectively. Pantoprazole sodium is widely used in treatment of acid-related disorders and management of gastroesophageal reflux diseases. It is an acid-labile drug that degrades in the stomach at pH 1-2 and is highly unstable in UVC light. Hence the aim of research work was to improve photostability of pantoprazole and protect it from the acidic environment by loading in gastroresistant microparticles. Various batches of microparticles were prepared by the solvent evaporation method using Eudragit S 100 as an enteric polymer that solubilizes at pH 7. Developed microparticles were characterized for different parameters and the formulation showing the highest drug entrapment was selected for photodegradation studies. Photodegradation studies were performed in solar light and in UV light at 254 nm and 366 nm for 7 days. The concentration of drug was determined spectrophotometrically at 290 nm. The percent degradation under solar light for pure drug was 25% and no significant degradation was seen in drug-loaded microparticles. Degradation under UV radiation 254 nm and 366 nm was found to be 38.6% and 12.11% and 35.11% and 6.13% for pure drug and drug-loaded microparticles, respectively. Microencapsulation decreases the penetration as well as absorption of radiation, which enhances the protection of pantoprazole sodium.

Rabeprazole for the treatment of acid-related disorders

Proton pump inhibitors are widely used for the treatment of acid-related disorders. Rabeprazole is a potent and irreversible inhibitor of H+/K+-ATPase gastric pump, and it is indicated for the treatment of gastroesophageal reflux disease, Zollinger Ellison syndrome, duodenal and gastric ulcers and for the eradication of Helicobacter pylori in combination with antibiotics. Pharmacokinetic and pharmacodynamic data show that rabeprazole achieves a pronounced acid suppression from the first administration that is maintained with repeated use; this may translate into faster onset of symptom relief for patients, particularly suitable when the indication is for the on-demand long-term maintenance of gastroesophageal reflux disease. Due to its predominantly nonenzymatic metabolism, rabeprazole has a lower potential for drug–drug interactions. The objective of this article is to update efficacy and safety data of rabeprazole in the treatment of acid-related disorders, following a previous review dated 2008.

Proton pump inhibitors prescribing following the introduction of generic drugs

In many countries, the introduction of generic proton pump inhibitors (PPIs) onto the pharmaceutical market increased the phenomenon of therapeutic substitution in acid-related disorders (ARDs). To investigate the treatment of ARDs in an Italian primary care setting from 2005 to 2008 by verifying: (i) dynamics of PPI prescribing; (ii) predictors of PPI switching; and (iii) healthcare resource consumption costs. This was a retrospective cohort study of 102 general practitioners (GPs) who managed an average of 150000 inhabitants in Naples. Multilevel logistic regression was used to assess the potential predictors of both PPI switching and termination. Primary care costs were expressed as the cost of ARD management per PPI user year. The percentage of PPI users with ARD increased from 5·5% (2005) to 7·0% (2008) (P<0·0001), especially for dyspepsia (from 9·5% to 13·7%; P<0·0001) and chronic treatments (from 23·4% to 29·4%; P<0·0001). PPI switching rose from 13·0% to 16·7% during the period observed (P<0·0001). Calendar years, long-term treatments and gastroesophageal reflux disease were positive predictors of PPI switching. Primary care costs relating to PPI switchers increased by 61·14€ compared with nonswitchers (P<0·0001). The introduction of generic PPIs onto the Italian market was associated with an increasing amount of PPI prescribing related to chronic treatments, unlicensed indications (e.g. dyspespsia) and therapeutic substitutions. Growing overall costs linked to the phenomenon of PPI switching was also found. Our data support the need to assess the effects of the introduction of generic drugs on both clinical outcomes and the cost management of ARDs.

Efficacy of Oral Famotidine and 2 Omeprazole Formulations for the Control of Intragastric pH in Dogs

Little is known about the efficacy of commonly used acid suppressants on intragastric pH in dogs. To compare the effect of oral famotidine, 2 formulations of omeprazole, and placebo on intragastric pH in dogs with a catheter-free, continuous pH monitoring system. Six healthy adult mixed-breed colony dogs. Utilizing a randomized, 4-way cross over, open-label study, dogs were administered famotidine PO (1.0-1.3 mg/kg q12h), omeprazole tablet (1.5-2.6 mg/kg q24h), omeprazole reformulated paste (RP) (Gastrogard, 1.5-2.6 mg/kg q24h), and placebo for 7 days followed by a 10-day washout period. Radiotelemetric pH capsules were placed with gastroscopy assistance to continuously record intragastric pH for 4 days (days 4-7 of dosing). The percentage of time that intragastric pH was ≥3 and ≥4 was compared among treatment groups using repeated measures of analysis of variance. Tukey's Studentized range test was used to determine which groups were different with α= 0.05. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 22 ± 8% and 14 ± 6% for famotidine, 63 ± 14% and 52 ± 17% for omeprazole tablet, 54 ± 17% and 44 ± 18% for omeprazole RP, and 6 ± 6% and 5 ± 5% for placebo. Both omeprazole formulations significantly increased intragastric pH compared with famotidine and placebo, but omeprazole tablet and RP was not significantly different from each other. Oral omeprazole tablet and RP provide superior gastric acid suppression to famotidine, and should therefore be considered more effective for the treatment of acid related disorders in dogs.

Pantoprazole

Pantoprazole is a proton pump inhibitor (PPI) that binds irreversibly and specifically to the proton pump, thereby reducing gastric acid secretion. Pantoprazole has a relatively long duration of action compared with other PPIs, and a lower propensity to become activated in slightly acidic body compartments. To date, no drug-drug interactions have been identified with pantoprazole in numerous interaction studies. Overall, in the short-term (8-10 weeks) initial treatment of gastro-oesophageal reflux disease (a condition that occurs when the reflux of gastric contents causes troublesome symptoms and/or complications) and long-term (6-24 months) maintenance therapy, oral pantoprazole 20 or 40 mg/day demonstrated similar efficacy to omeprazole, lansoprazole and esomeprazole and greater efficacy than histamine type 2 receptor antagonists. Pantoprazole is also effective in treating and preventing NSAID-related gastric and gastroduodenal injury. The optimal adult oral dose for gastric acid-related disorders is pantoprazole 40 mg once daily. Although data are limited, pantoprazole 20 or 40 mg/day was effective and well tolerated in the treatment of acid-related disorders in children and adolescents. Pantoprazole was also well tolerated in adults with acid-related disorders in short- and long-term studies. Thus, pantoprazole is a valuable agent for the management of acid-related disorders.

Review article: building an algorithm for the management of geriatric acid-related disorders in Asia

The special needs of the elderly must be considered in the treatment of acid-related disorders in older patients. Workshop participants discussed the Genval workshop report algorithm as a step toward building a consensus on the management of elderly patients in Asia. The consensus reached is summarized as follows: (i) old age alone is an indication for endoscopic investigation of reflux symptoms; (ii) elderly patients should undergo endoscopy when they present with acid reflux symptoms; (iii) a biopsy-based test for Helicobacter pylori should be performed if endoscopy is done, and eradication of H. pylori is warranted as it will reduce the risk of peptic ulcers and may retard the progression of early precancerous gastric lesions; (iv) it is not recommended to routinely take additional biopsies for histology in patients with H. pylori infection in the absence of any macroscopic suspicious lesions; (v) patients with reflux disease LA grade B or below should be started on a standard-dose proton pump inhibitor for 4-8 weeks, and then followed by step-down to on-demand therapy; (vi) patients with LA grade C or above reflux oesophagitis should be initially given standard-dose proton pump inhibitor therapy for at least 8 weeks and then continue with maintenance proton pump inhibitor therapy.

Review article: exploring strategies to improve treatment outcomes and compliance in specific patient groups with acid?related disorders

Specific patient groups consisting of those with nasogastric or gastrostom feeding tubes such as those with stroke neurological impairment or other etiologies, patients with difficulty swallowing (i.e. oral pharyngeal dysfunction), unconscious patients and children who dislike or refuse taking or cannot swallow tablets require special attention with regard to the pharmacological treatment of acid-related disorders. In particular, these groups of patients require special formulations in order to achieve optimal compliance with acid suppression therapy. Formulations such as the syrup histamine (H 2 )-receptor antagonist in a syrup formulation, or for proton pump inhibitors, either the multiple unit pellet capsules, fast dissolving tablets or intravenous formulations, can be used to overcome swallowing problems or bitter taste.

Sodium pantoprazole-loaded enteric microparticles prepared by spray drying: Effect of the scale of production and process validation

Pantoprazole is a prodrug used in the treatment of acid related disorders and Helicobacter pylori infections. It is activated inside gastric parietal cells binding irreversibly to the H +/K +-ATPase. In this way, pantoprazole must be absorbed intact in the intestinal tract, which indicates that enteric drug delivery systems are required for its oral administration. The purpose of this study was to investigate the physical characteristics of enteric pantoprazole-loaded microparticles prepared by spray drying using a blend of Eudragit S100 ® and HPMC. The microparticles were produced in different spray dryers and operational conditions at laboratory and pilot scales. Microparticles produced with two fluid nozzle atomizer and air pressure of 196 kPa presented satisfactory encapsulation efficiency and gastro-resistance. Microparticles produced with the same atomizer but using 49 kPa of air pressure presented strings in the powder. The microparticles produced in mixed flow presented very high polydispersity and the ones produced with rotating disc atomizer presented drug crystals adsorbed on the particle surfaces. The microparticles produced with two fluid nozzle atomizer and 196 kPa were prepared in three consecutive days for the process validation. The powders showed reproducible diameter, polydispersity, densities, encapsulation efficiency and gastro-resistance profile.

Preparation, characterization, and in vivo anti-ulcer evaluation of pantoprazole-loaded microparticles

Pantoprazole is an important drug in the treatment of acid-related disorders. This work concerns the preparation and characterization of gastro-resistant pantoprazole-loaded microparticles prepared using an O/O emulsification/solvent evaporation technique. The in vivo activity of the pantoprazole-loaded Eudragit ® S100 microparticles was carried out in rats. Furthermore, tablets containing the microparticles were also investigated. Microparticles presented spherical and smooth morphologies (SEM) and they remained intact in the inner surface of tablets. DSC and IR analyses showed that pantoprazole was physically and molecularly dispersed in the polymer. In vivo anti-ulcer evaluation showed that the microparticles were able to protect rat stomachs against ulcer formation, while the drug aqueous solution did not present activity. Drug dissolution profiles from tablets demonstrated slower release than untabletted microparticles. Weibull equation was the best model for describing the drug release profiles from microparticles and tablets. As regards the acid protection, tablets showed a satisfactory drug protection in acid medium (61.05 ± 8.09% after 30 min).

CYP2C19 genotype and the PPIs – focus on rabeprazole

Amongst all the proton pump inhibitors (PPI), the hepatic metabolism of rabeprazole is least dependent on the CYP4502C19 system. Rabeprazole is therefore the PPI least affected by CYP4502C19 genetic polymorphism. This unique feature of rabeprazole complements rabeprazole's fast onset of action, and may lead to profound and consistent inhibition of gastric acid secretion in the treatment of acid-related disorders.