Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longer-acting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.
Gastroesophageal Reflux ; Metabolism ; Peptic Ulcer ; Pharmacokinetics ; Plasma ; Proton Pump Inhibitors* ; Proton Pumps* ; Protons* ; Rabeprazole ; United States Food and Drug Administration

The prevalence of gastoesophageal reflux disease (GERD) has been rapidly increased in Korea during last 20 years. However, there has been no systematic review regarding this disease. The aim of this article was to provide a review of available diagnostic modalities for GERD. This review includes proton pump inhibitor (PPI) test, endoscopy, ambulatory pH monitoring, impedance pH monitoring, and esophageal manometry in order to provide a basis for the currently applicable recommendations in the diagnosis of GERD in Korea. With weekly heartburn or acid regurgitation, the prevalence of GERD has been reported as 3.4% to 7.9%, indicating an increase of GERD in Korea. As the prevalence of Barrett's esophagus has been reported to be low, the screening endoscopy for Barrett's esophagus is not recommended. Several recent meta-analyses re-evaluated the value of the PPI test in patients with typical GERD symptoms and non-cardiac chest pain. That is, the PPI test has been proven to be a sensitive tool for diagnosing GERD in patients with non-cardiac chest pain and in some preliminary trials regarding extraesophageal manifestations of GERD. Ambulatory pH monitoring of the esophagus helps to confirm gastroesophageal reflux in patients with persistent symptoms (both typical and atypical) in the absence of esophageal mucosal damage, especially when a trial of acid suppression has failed. Impedance pH test is useful in refractory reflux patients with primary complaints of typical GERD symptoms, but this value has not been proved in patients with non-cardiac chest pain or extraesophageal symptoms. This systematic review is targeted to establish the strategy of GERD diagnosis, which is essential for the current clinical practice.
Barrett Esophagus/diagnosis ; Esophageal pH Monitoring ; Gastroesophageal Reflux/*diagnosis/epidemiology ; Humans ; Manometry ; Proton Pump Inhibitors/metabolism ; Risk Factors

The prevalence of gastoesophageal reflux disease (GERD) has been rapidly increased in Korea during last 20 years. However, there has been no systematic review regarding this disease. The aim of this article was to provide a review of available diagnostic modalities for GERD. This review includes proton pump inhibitor (PPI) test, endoscopy, ambulatory pH monitoring, impedance pH monitoring, and esophageal manometry in order to provide a basis for the currently applicable recommendations in the diagnosis of GERD in Korea. With weekly heartburn or acid regurgitation, the prevalence of GERD has been reported as 3.4% to 7.9%, indicating an increase of GERD in Korea. As the prevalence of Barrett's esophagus has been reported to be low, the screening endoscopy for Barrett's esophagus is not recommended. Several recent meta-analyses re-evaluated the value of the PPI test in patients with typical GERD symptoms and non-cardiac chest pain. That is, the PPI test has been proven to be a sensitive tool for diagnosing GERD in patients with non-cardiac chest pain and in some preliminary trials regarding extraesophageal manifestations of GERD. Ambulatory pH monitoring of the esophagus helps to confirm gastroesophageal reflux in patients with persistent symptoms (both typical and atypical) in the absence of esophageal mucosal damage, especially when a trial of acid suppression has failed. Impedance pH test is useful in refractory reflux patients with primary complaints of typical GERD symptoms, but this value has not been proved in patients with non-cardiac chest pain or extraesophageal symptoms. This systematic review is targeted to establish the strategy of GERD diagnosis, which is essential for the current clinical practice.
Barrett Esophagus/diagnosis ; Esophageal pH Monitoring ; Gastroesophageal Reflux/*diagnosis/epidemiology ; Humans ; Manometry ; Proton Pump Inhibitors/metabolism ; Risk Factors

The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.
Anti-Ulcer Agents/therapeutic use ; Cytochrome P-450 CYP2C19/genetics ; Esophageal pH Monitoring ; Gastroesophageal Reflux/drug therapy/metabolism/*pathology ; Genotype ; Heartburn ; Humans ; Proton Pump Inhibitors/therapeutic use

Belching is a normal physiological function that may occur when ingested air accumulated in the stomach is expelled or when food containing air and gas produced in the gastrointestinal tract is expelled. Excessive belching can cause patients to complain of abdominal discomfort, disturbed daily life activities, decreased quality of life and may be related to various gastrointestinal disorders such as gastroesophageal reflux disease, functional dyspepsia, aerophagia and rumination syndrome. Belching disorders can be classified into aerophagia and unspecified belching disorder according to the Rome III criteria. Since the introduction of multichannel intraluminal impedance monitoring, efforts are being made to elucidate the types and pathogenic mechanisms of belching disorders. Treatment modalities such as behavioral therapy, speech therapy, baclofen, tranquilizers and proton pump inhibitors can be attempted, but further investigations on the effective treatment of belching disorders are warranted.
Aerophagy ; Behavior Therapy ; Eructation/metabolism/*pathology/therapy ; Humans ; Muscle Relaxants, Central/therapeutic use ; Proton Pump Inhibitors/therapeutic use ; Quality of Life ; Speech Therapy

Eosinophilic esophagitis (EoE) with adults, as a new disease emerging during the last decade, is a clinicopathologic disorder of the esophagus characterized by a dense esophageal eosinophilic infiltration and typical esophageal symptoms. As numerous studies about EoE had been reported during last several years, updated consensus of EoE was reported in July 2011. The conceptual definition of EoE is coming. EoE is defined as a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominat inflammation. Other important addition is genotyping feature that implicates thymic stromal lymphopoietin genes or filagrrin as EoE susceptibility genes. The majority of patients has the concurrent allergic disease, especially food or aeroallergen sensitization. Main therapeutic options include topical steroids and dietary modification. Recent issues of EoE include a new concept for proton pump inhibitor-responsive esophageal eosinophilia that it should be excluded to diagnose EoE.
Diet ; Endoscopy, Gastrointestinal ; Eosinophilic Esophagitis/*diagnosis/pathology/therapy ; Esophagus/surgery ; Humans ; Hydrogen-Ion Concentration ; Hypersensitivity/immunology ; Immunoglobulin E/metabolism ; Proton Pump Inhibitors/therapeutic use ; Steroids/therapeutic use

Clinical studies reported hypomagnesaemia in long-term omeprazole usage that was probably due to intestinal Mg2+ wasting. Our previous report demonstrated the inhibitory effect of omeprazole on passive Mg2+ transport across Caco-2 monolayers. The present study aimed to identify the underlying mechanism of omeprazole suppression of passive Mg2+ absorption. By using Caco-2 monolayers, we demonstrated a potent inhibitory effect of omeprazole on passive Mg2+, but not Ca2+, transport across Caco-2 monolayers. Omeprazole shifted the %maximum passive Mg2+ transport-Mg2+ concentration curves to the right, and increased the half maximal effective concentration of those dose-response curves, indicating a lower Mg2+ affinity of the paracellular channel. By continually monitoring the apical pH, we showed that omeprazole suppressed apical acid accumulation. Neomycin and spermine had no effect on passive Mg2+ transport of either control or omeprazole treated monolayers, indicating that omeprazole suppressed passive Mg2+ transport in a calcium sensing receptor (CaSR)-independent manner. The results of western blot analysis showed that omeprazole significantly suppressed claudin (Cldn)-7 and -12, but not Cldn-2, expression in Caco-2 cells. By using apical solution of pH 5.5, 6.0, 6.5, and 7.0, we found that apical acidity markedly increased passive Mg2+ transport, Mg2+ affinity of the paracellular channel, and Cldn-7 and -12 expression in Caco-2 monolayers. Apical acidity abolished the inhibitory effect of omeprazole on passive Mg2+ transport and Cldn-7 and -12 expression. Our results provided the evidence for the regulation of intestinal passive Mg2+ absorption by luminal acidity-induced increase in Cldn-7 and -12 expression.
Absorption/drug effects ; Caco-2 Cells ; Calcium/metabolism ; Claudins/genetics/*metabolism ; Dose-Response Relationship, Drug ; Gene Expression/drug effects ; Humans ; Hydrogen-Ion Concentration ; Magnesium/*metabolism ; Omeprazole/*pharmacology ; Proton Pump Inhibitors/*pharmacology ; Receptors, Calcium-Sensing/metabolism

OBJECTIVETo investigate the impact of omeprazole on platelet response to clopidogrel and the effect of polymorphisms of CYP2C19 on the antiplatelet effect of clopidogrel.

METHODSPlatelet aggregation (PA) was assessed before 300 mg aspirin plus 300 mg loading dose of clopidogrel and after 300 mg aspirin plus 75 mg maintenance dose of clopidogrel 7 days later in 414 patients with acute coronary syndrome who have undergone percutaneous coronary intervention (PCI). Thereafter, gastric mucosal protective drugs were given (omeprazolem 20 mg, n=224 or cimetidine 800 mg, n=190). Fourteen days later, PA was measured again. Genotypes of CYP2C19*2 were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

RESULTSAfter taken aspirin and clopidogrel, PA has decreased significantly in both groups. Compared with cimetidine, omeprazole had no significant impact on PA on 7 and 21 days post PCI. Compared with homozygotes or heterozygotes for the wild-type CYP2C19*2, patients with CYP2C19*2 AA genotype had significantly higher PA on 7 and 21 days post PCI (P<0.05).

CONCLUSIONNo attenuating effect on platelet response to clopidogrel has been observed for Omeprazole. The variant of CYP2C19*2 AA genotype is significantly associated with attenuated response to clopidogrel.

Adult ; Aged ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP2C19 ; Drug Interactions ; Female ; Humans ; Male ; Middle Aged ; Omeprazole ; pharmacology ; Platelet Aggregation Inhibitors ; pharmacology ; Proton Pump Inhibitors ; pharmacology ; Ticlopidine ; analogs & derivatives ; pharmacology

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) act by irreversibly binding to the H+-K+-ATPase of the proton pump in parietal cells and may possibly affect the vacuolar H+-ATPase in osteoclasts. METHODS: We investigated the effect of 8 weeks of PPI treatment on the parameters of bone turnover and compared PPI with revaprazan, which acts by reversibly binding to H+-K+-ATPase in proton pumps. This study was a parallel randomized controlled trial. For 8 weeks, either a PPI or revaprazan was randomly assigned to patients with gastric ulcers. The parameters of bone turnover were measured at the beginning of and after the 8-week treatment period. RESULTS: Twenty-six patients (PPI, n=13; revaprazan, n=13) completed the intention-to-treat analysis. After the 8-week treatment period, serum calcium and urine deoxypyridinoline (DPD) were increased in the PPI group (serum calcium, p=0.046; urine DPD, p=0.046) but not in the revaprazan group. According to multivariate linear regression analysis, age > or =60 years was an independent predictor for the changes in serum calcium and urine DPD. CONCLUSIONS: In elderly patients, administering a PPI for 8 weeks altered bone parameters. Our study suggested that PPIs might directly alter bone metabolism via the vacuolar H+-ATPase in osteoclasts.
Aged ; Amino Acids/drug effects/urine ; Bone Remodeling/*drug effects ; Bone and Bones/*metabolism ; Calcium/blood ; Female ; Humans ; Intention to Treat Analysis ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Osteoclasts/*metabolism ; Prospective Studies ; Proton Pump Inhibitors/*pharmacology ; Pyrimidinones/*pharmacology ; Tetrahydroisoquinolines/*pharmacology

OBJECTIVE: To evaluate the efficacy of proton pump inhibitor (PPI) therapy with esomeprazole on laryngopharyngeal reflux (LPR) by pepsin immunoassay in the sputum. METHOD: From June 2009 to March 2010, patients in the ENT outpatient department of Nanfang hospital with a reflux finding score (RFS) >7 and a reflux symptom index (RSI) >13 were selected. Their sputum was obtained in the morning for pepsin assay. Twenty-six patients with positive results of pepsin assay were enrolled and received esomeprazole 20 mg twice daily for two months. They paid return visits every two weeks. RSI, RFS and pepsin concentration in the sputum were assessed at baseline and after two months. Pepsin in the sputum was measured by enzyme linked immunoadsorbent assay. RESULT: After 8 weeks, 24 patients got symptom improvements except 2. All got improved results of laryngoscope exams. RSI and RFS scores before and after PPI treatment reached statistical signification by paired t-test (t= 8.152, P<0.01; t=9.704, P<0.01). 21 patients' pepsin concentrations decreased except 5. Nonparametric tests were used because the reduction of pepsin concentrations before and after PPI treatment were not normally distributed (Z=-3.213, P<0.01). Reductions of total RSI and RFS scores as well as pepsin concentrations were significantly higher after two months. CONCLUSION Twice-daily PPI treatment for two months demonstrated a significantly greater improvement in laryngeal appearance and LPR symptoms for most patients in this study, which can result in significantly decreased levels of pepsin in sputum.
Adolescent ; Adult ; Esomeprazole ; therapeutic use ; Female ; Humans ; Laryngopharyngeal Reflux ; drug therapy ; metabolism ; Male ; Middle Aged ; Pepsin A ; metabolism ; Prospective Studies ; Proton Pump Inhibitors ; therapeutic use ; Sputum ; chemistry ; Treatment Outcome ; Young Adult