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At least 19 recordsLinked to original sources

PubMed2006

Review article: the clinical pharmacology of proton pump inhibitors.

Proton pump inhibitors inhibit the gastric H+/K+-ATPase via covalent binding to cysteine residues of the proton pump. All proton pump inhibitors must undergo acid accumulation in the parietal cell through protonation, followed by activation mediated by a second protonation at the active secretory canaliculus of the parietal cell. The relative ease with which these steps occur with different proton pump inhibitors underlies differences in their rates of activation, which in turn influence the location of covalent binding and the stability of inhibition. Slow activation is associated with binding to a cysteine residue involved in proton transport that is located deep in the membrane. However, this is inaccessible to the endogenous reducing agents responsible for restoring H+/K+-ATPase activity, favouring a longer duration of gastric acid inhibition. Pantoprazole and tenatoprazole, a novel proton pump inhibitor which has an imidazopyridine ring in place of the benzimidazole moiety found in other proton pump inhibitors, are activated more slowly than other proton pump inhibitors but their inhibition is resistant to reversal. In addition, tenatoprazole has a greatly extended plasma half-life in comparison with all other proton pump inhibitors. The chemical and pharmacological characteristics of tenatoprazole give it theoretical advantages over benzimidazole-based proton pump inhibitors that should translate into improved acid control, particularly during the night.

Antacids↗

PubMed2000

Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors.

Proton pump inhibitors have dramatically influenced the management of acid-peptic disorders in recent years. They all have a broadly similar mechanism of action and are extensively metabolized in the liver via cytochromes P450 2C19 and 3A4. There is some variation in their potential for drug interactions due to differences in enzyme inhibition. Relatively few serious adverse effects have been reported for the proton pump inhibitors. Comparative studies of acid suppression suggest that lansoprazole and pantoprazole have a potency similar to that of omeprazole on a mg for mg basis; however, rabeprazole may have a greater potency than omeprazole. Lansoprazole and rabeprazole display a more rapid onset of maximal acid suppression than the other proton pump inhibitors. Comparative studies using proton pump inhibitors for the treatment of reflux oesophagitis, duodenal ulcer healing and Helicobacter pylori eradication show little overall difference in outcome between the proton pump inhibitors when used in their standard doses. Lansoprazole and rabeprazole provide earlier and better symptom relief than the other proton pump inhibitors in some studies of peptic ulcer treatment. The few studies of gastric ulcer treatment suggest that there is an advantage in using the proton pump inhibitors that have a higher standard daily dose.

Duodenal Ulcer↗

PubMed2006

Pharmacokinetic drug interaction profiles of proton pump inhibitors.

Proton pump inhibitors are used extensively for the treatment of gastric acid-related disorders because they produce a greater degree and longer duration of gastric acid suppression and, thus, better healing rates, than histamine H(2) receptor antagonists. The need for long-term treatment of these disorders raises the potential for clinically significant drug interactions in patients receiving proton pump inhibitors and other medications. Therefore, it is important to understand the mechanisms for drug interactions in this setting. Proton pump inhibitors can modify the intragastric release of other drugs from their dosage forms by elevating pH (e.g. reducing the antifungal activity of ketoconazole). Proton pump inhibitors also influence drug absorption and metabolism by interacting with adenosine triphosphate-dependent P-glycoprotein (e.g. inhibiting digoxin efflux) or with the cytochrome P450 (CYP) enzyme system (e.g. decreasing simvastatin metabolism), thereby affecting both intestinal first-pass metabolism and hepatic clearance. Although interactions based on the change of gastric pH are a group-specific effect and thus may occur with all proton pump inhibitors, individual proton pump inhibitors differ in their propensities to interact with other drugs and the extent to which their interaction profiles have been defined. The interaction profiles of omeprazole and pantoprazole have been studied most extensively. A number of studies have shown that omeprazole carries a considerable potential for drug interactions, since it has a high affinity for CYP2C19 and a somewhat lower affinity for CYP3A4. In contrast, pantoprazole appears to have lower potential for interactions with other medications. Although the interaction profiles of esomeprazole, lansoprazole and rabeprazole have been less extensively investigated, evidence suggests that lansoprazole and rabeprazole seem to have a weaker potential for interactions than omeprazole. Although only a few drug interactions involving proton pump inhibitors have been shown to be of clinical significance, the potential for drug interactions should be taken into account when choosing a therapy for gastric acid-related disorders, especially for elderly patients in whom polypharmacy is common, or in those receiving a concomitant medication with a narrow therapeutic index.

Anti-Ulcer Agents↗

PubMed2000

New perspectives in gastric acid suppression: genetic polymorphisms predict the efficacy of proton pump inhibitors.

Proton pump inhibitors are highly effective in the management of acid-peptic diseases. These drugs potently inhibit acid secretion from gastric parietal cells by irreversibly inhibiting activity of the H(+), K(+) ATPase (proton pump). Early studies of the pharmacokinetics of proton pump inhibitors demonstrated considerable variation in drug clearance rates among patients and healthy volunteers. This variation was also reflected in a wide range of the efficacy of acid suppression by standard doses of proton pump inhibitors among study subjects; those with slower clearance and higher drug concentrations experienced superior acid suppression. Proton pump inhibitors are predominantly inactivated by the 2C19 isoform of the hepatic cytochrome P450 mixed function oxidase system. The cytochrome P450 2C19 gene is polymorphic, with three known inactivating mutations. Individuals with one or two mutant cytochrome P450 2C19 alleles metabolize proton pump inhibitors more slowly than those with two wild-type alleles and experience higher drug levels. An individual's cytochrome P450 2C19 genotype predicts the degree of acid suppression in response to a standard dose of a proton pump inhibitor. Emerging data suggests that the clinical effectiveness of proton pump inhibitors in the treatment of acid-peptic diseases may also be dependent on cytochrome P450 2C19 genotype.

Cytochrome P-450 Enzyme System↗

PubMed2004

CYP2C19 polymorphism and proton pump inhibitors.

Proton pump inhibitors such as omeprazole (esomeprazole), lansoprazole, pantoprazole and rabeprazole are eliminated by the hepatic route and the polymorphic CYP2C19 is mainly involved in their metabolism. In different populations three phenotypes have been identified: extensive metabolizers, poor metabolizers and individuals carrying one wild type and one mutant allele (het extensive metabolizers). Systemic exposure to the proton pump inhibitors as expressed by the AUC (area under the plasma level time profiles) is 5-12-times higher in poor metabolizers than in extensive metabolizers. As the pharmacodynamic response (elevation of intragastric pH) to the proton pump inhibitors is related directly to their AUC, a much higher pH can be monitored over 24 hr in poor metabolizers than in extensive metabolizers. Furthermore, clinical efficacy of all proton pump inhibitors depend on maintaining intragastric pH above certain threshold levels and significantly higher eradication rates of Helicobacter pylori have been observed in patients of the poor metabolizers and het extensive metabolizers phenotype if compared to extensive metabolizers. Likewise, limited data suggest that proton pump inhibitors-induced healing rates in gastro-oesophageal reflux disease are apparently higher in poor metabolizers/het extensive metabolizers than in extensive metabolizers of CYP2C19. Therefore initial genotyping for this enzyme and higher dosage in extensive metabolizers is likely to improve the clinical efficacy of proton pump inhibitors.

Anti-Ulcer Agents↗

PubMed2001

Problems associated with the clinical use of proton pump inhibitors.

Proton pump inhibitors have proven to be important in the treatment of acid/peptic diseases. However, their therapeutic uses have extended over time, which may alter their risk:benefit ratio. Significant rebound acid hypersecretion has been demonstrated, which persists for at least two months. Its clinical significance remains unknown. Enhanced oxyntic gastritis may be responsible for the increased acid suppressive effects of proton pump inhibitors in H. pylori-infected patients. It remains unclear whether either H. pylori eradication or diminishing rates of infection in the developed world will therefore decrease the efficacy of proton pump inhibitors. Problems with carcinoids in rodents have not been found in man. However, the consequences of very long-term use of proton pump inhibitors remain unknown. Similarly, the development of atrophic gastritis in H. pylori-positive patients treated with proton pump inhibitors, with the long-term concern of gastric carcinoma development, remains controversial.

Animals↗

PubMed2004

Pharmacogenomics of proton pump inhibitors.

Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are metabolized by cytochrome P450 isoenzyme 2C19 (CYP2C19) in the liver. There are genetic differences that affect the activity of this enzyme. The genotypes of CYP2C19 are classified into three groups: homozygous extensive metabolizer (homEM), heterozygous extensive metabolizer (hetEM), and poor metabolizer (PM). The pharmacokinetics and pharmacodynamics of PPIs differ among the different CYP2C19 genotype groups. Plasma PPI and intragastric pH levels during PPI treatment are the lowest in the homEM group and the highest in the PM group. These CYP2C19 genotype-dependent differences in pharmacokinetics and pharmacodynamics of PPIs are reflected in the cure rates for gastroesophageal reflux disease and Helicobacter pylori infection with PPI-based therapies. The CYP2C19 genotyping test is a useful tool for deciding on the optimal treatment regimen using a PPI, including a dual (PPI plus antibiotic) or a triple (PPI plus two antibiotics) therapy.

Anti-Bacterial Agents↗

PubMed1992

[Endoscopic stage classification of peptic ulcer and characterization of the healing process by proton pump inhibitors].

Proton pump inhibitors are highly effective for gastric acid secretion and have been shown to be superior to histamine H2-receptor antagonists. The superiority of proton pump inhibitors over H2-receptor antagonists was more pronounced in duodenal ulcers. Omeprazole reduced the time required by H2-receptor antagonists the healing of duodenal ulcers by 2/3 to 1/2. On the other hand, unusual endoscopic findings, such as shallow white coat or protrusion of the ulcer floor, were noted in the healing stage of gastric ulcers with H2-receptor antagonists. Whereas these findings were rarely seen with conventional drugs. Histologically, the protrusion was made up granulation tissue consisting of cell infiltration and renewed capillaries with or without regenerated epithelia. These unusual endoscopic findings may be observed in the peptic ulcers treated with proton pump inhibitors.

Adenosine Triphosphatases↗

PubMed2001

[Comparative study of proton pump inhibitors].

Proton pump inhibitors (PPI) have influenced dramatically the management of acid-related disorders in recent years. They all have a broadly similar mechanism of action. There are some differences however, between the PPIs in their pharmacokinetics, pharmacodynamics, clinical efficacy, and potential for drug interactions. Although the individual PPI have similar efficacy in many cases, differences between them should be considered when choosing a treatment regimen. Further clinical trials are needed to assess the clinical importance of these differences, as well as to assess whether the potential advantages result in clinical benefit for patients with acid-related disorders.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

Chemistry of covalent inhibition of the gastric (H+, K+)-ATPase by proton pump inhibitors.

Proton pump inhibitors (PPIs), drugs that are widely used for treatment of acid related diseases, are either substituted pyridylmethylsulfinyl benzimidazole or imidazopyridine derivatives. They are all prodrugs that inhibit the acid-secreting gastric (H(+), K(+))-ATPase by acid activation to reactive thiophiles that form disulfide bonds with one or more cysteines accessible from the exoplasmic surface of the enzyme. This unique acid-catalysis mechanism had been ascribed to the nucleophilicity of the pyridine ring. However, the data obtained here show that their conversion to the reactive cationic thiophilic sulfenic acid or sulfenamide depends mainly not on pyridine protonation but on a second protonation of the imidazole component that increases the electrophilicity of the C-2 position on the imidazole. This protonation results in reaction of the C-2 with the unprotonated fraction of the pyridine ring to form the reactive derivatives. The relevant PPI pK(a)'s were determined by UV spectroscopy of the benzimidazole or imidazopyridine sulfinylmethyl moieties at different medium pH. Synthesis of a relatively acid stable analogue, N(1)-methyl lansoprazole, (6b), allowed direct determination of both pK(a) values of this intact PPI allowing calculation of the two pK(a) values for all the PPIs. These values predict their relative acid stability and thus the rate of reaction with cysteines of the active proton pump at the pH of the secreting parietal cell. The PPI accumulates in the secretory canaliculus of the parietal cell due to pyridine protonation then binds to the pump and is activated by the second protonation on the surface of the protein to allow disulfide formation.

Animals↗

PubMedDate not supplied

Anaphylaxis to proton pump inhibitors.

Proton pump inhibitors (PPI) are widely used for the treatment of peptic ulcer, but cases of anaphylactic reactions have rarely been described. We present a patient who experienced an episode of urticaria 30 minutes after oral intake of an omeprazole capsule. Skin prick tests to omeprazole, pantoprazole and lansoprazole were positive. Challenge test with lansoprazole was carried out and within 45 minutes the patient developed urticaria, facial edema, vomiting, and hypotension. Oral challenge with other imidazole derivatives (ketoconazole, cimetidine, metronidazole) were carried out with good tolerance. Serum tryptase levels determined 3 hours after the adverse reaction to lansoprazole were elevated. Specific IgE to PPI were not detected by an enzyme-linked immunosorbent assay technique. The clinical findings, positive skin prick test to PPI and elevated serum tryptase levels suggest that an IgE-mediated mechanism was implicated in the reactions to both omeprazole and lansoprazole. Skin prick tests may be a useful tool for detecting patients sensitized to PPI. An experimental protocol was used to detect specific IgE antibodies against PPI, which may explain RAST negativity. The previous findings suggest that cross-reactivity between PPI exists, but not with other imidazoles.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Shortcomings of the first-generation proton pump inhibitors.

Proton pump inhibitors (PPIs) are widely prescribed for the treatment of gastro-oesophageal reflux disease (GORD) as well as gastric and duodenal ulcers, and these agents are now considered the drugs of choice for managing such acid-related disorders. Despite their well-documented efficacy and safety, first-generation PPIs (omeprazole, pantoprazole and lansoprazole) have notable limitations. These drugs exhibit substantial interpatient variability in pharmacokinetics and may have significant interactions with other drugs. The time of dosing and ingestion of meals may also influence the pharmacokinetics of these agents as well as their ability to suppress gastric acid secretion. First-generation PPIs also have a relatively slow onset of pharmacological action and may require several doses to achieve maximum acid suppression and symptom relief, possibly limiting their usefulness in on-demand GORD therapy. First-generation PPIs may also fail to provide 24-h suppression of gastric acid, and noctural acid breakthrough can occur even with twice-daily dosing. Both first- and second-generation PPIs may be associated with adverse events consequent to gastric acid suppression, but newer PPIs have the potential to overcome some critical pharmacokinetic, pharmacodynamic, and clinical limitations of the first-generation drugs.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2002

Treatment of acid-related diseases in the elderly with emphasis on the use of proton pump inhibitors.

Proton pump inhibitors (PPIs) have revolutionised the treatment of acid-related disorders, and they have also made it possible to define the spectrum of acid inhibition required for optimal treatment in each disorder. Five PPIs are now available: the older drugs, omeprazole, lansoprazole and pantoprazole, and the two newest, rabeprazole and esomeprazole. These agents have predominantly been developed in the younger adult population, and data for the elderly population are limited. Subtle differences have emerged between the old and the new PPIs in their pharmacokinetic, pharmacodynamic and efficacy profiles. The degree of clinical relevance of these differences in the adult population is in question. However, according to this review, based on the available data for the elderly and by inference from the adult population, the differences are highly relevant in the elderly population. Studies of the pharmacokinetics of older PPIs demonstrated considerable variation in drug clearance that was reflected in a wide range of efficacy related to acid suppression with standard dosages. The newer PPIs offer several advantages over older agents, particularly in terms of rapid, profound and consistent acid inhibition. Consistent acid inhibition is particularly important in the elderly since clinical response is often difficult to judge in this patient group. An individual's cytochrome P450 (CYP) 2C19 genotype predicts the degree of acid suppression and consequently the clinical efficacy of the PPIs. The older PPIs are predominantly metabolised by CYP2C19, with this being of more importance for omeprazole and lansoprazole than pantoprazole. The hepatic metabolism of rabeprazole is predominantly by nonenzymatic reactions and minimally by CYP-mediated reactions, which therefore confers an advantage over older PPIs in that genetic polymorphisms for CYP2C19 do not significantly influence rabeprazole clearance, clinical efficacy or potential for drug interactions. The metabolism of esomeprazole involves CYP2C19 but to a lesser extent than its predecessor omeprazole. Furthermore, esomeprazole has a more rapid onset of action and less variation in clearance rates than omeprazole. Drug clearance decreases with age independently of CYP2C19 status, exaggerating some of the differences between the PPIs and increasing the risk of drug interactions.

Aged↗

PubMed2006

[Mechanism of actions and clinical applications of proton pump inhibitors].

Proton pump inhibitors (PPIs) are widely used in clinical practice from early 1990s for the treatment of acid- related diseases. PPIs are superior to histamine2-receptor antagonists or anticholinergic agents. These drugs have proven to be effective, safe and well-tolerated during the past two decades. This brief review presents the pharmacodynamics and pharmacokinetics of PPIs and presents clinical applications of the drugs in acid-related diseases.

Gastric Acid↗

PubMed2000

Does fasting serum gastrin predict gastric acid suppression in patients on proton-pump inhibitors?

Proton pump inhibitors (PPIs) block gastric acid secretion and may increase serum gastrin concentration. The aim of this study was to determine whether fasting serum gastrin concentration predicts gastric acid suppression in patients on PPI therapy. Ambulatory pH monitoring with one pH probe in the distal esophagus and a second probe in the stomach was performed in patients with persistent symptoms of GERD despite PPI treatment. Upon completion of pH monitoring, blood was drawn for measurement of fasting serum gastrin concentration. In all, 51 patients were studied: 26 on PPIs, 1 on H2-receptor antagonists, and 24 off acid suppression. Fasting serum gastrin correlated inversely with percent time of gastric pH < 4 for all patients (r = -0.553; P<0.001) and for the subgroup of 26 patients on PPIs (r = -0.435; P = 0.027). In patients on PPIs, an elevated gastrin (> or =100 pg/ml) was associated with gastric pH < 4 for 25+/-7% of the time compared to 54+/-5% when the gastrin was normal (P = 0.004). Therapeutic gastric acid suppression (gastric pH < 4 for <50% of time) was present in 6 of 7 (86%) patients with an elevated fasting serum gastrin, compared with only 8 of 19 (42%) patients with a normal serum gastrin (P<0.05). In conclusion, there is a significant inverse correlation between the fasting serum gastrin concentration and gastric acid profile in patients with GERD. An elevated fasting serum gastrin concentration while on PPI therapy suggests that gastric acid secretion is adequately suppressed.

Fasting↗

PubMed2001

Bedtime H2 blockers improve nocturnal gastric acid control in GERD patients on proton pump inhibitors.

AIM: Proton pump inhibitors taken twice daily before meals (proton pump inhibitor b.d. AC) effectively controls daytime gastric pH; however, nocturnal gastric acid breakthrough (NAB) occurs in more than 75% of patients. Adding an H2-blocker at bedtime decreases NAB in normal subjects. The efficacy of this regimen has not been evaluated in GERD patients. The aim of this study was to assess the effects of proton pump inhibitor b.d., both with and without bedtime H2-blocker on intragastric pH and the occurrence of NAB in GERD patients. METHODS: Prolonged ambulatory pH studies in GERD patients were reviewed. Group A: 60 patients (mean age 53 years, male 30) taking either omeprazole 20 mg or lansoprazole 30 mg b.d. Group B: 45 patients (mean age 49 years, male 23) on proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) plus an H2-blocker at bedtime (ranitidine 300 mg, famotidine 40 mg or nizatidine 300 mg). Eleven patients were evaluated during treatment with both regimens (group C). The percentage time of nocturnal and daytime intragastric pH > 4 and per cent of patients with gastric NAB were analysed. In the patients with NAB, its duration and associated oesophageal acid exposure also were analysed. RESULTS: Median percentage time intragastric pH > 4 overnight was 51% in group A, compared to 96% in group B (P < 0.0001). Median percentage daytime pH > 4 was 73% in group A and 79.8% in group B (P=0.14). Median percentage time intragastric pH >p 4 overnight increased from 54.6% without H2RA to 96.5% after adding bedtime H2RA (P=0.0013) in group C patients. NAB occurred in 82% patients in group A and 40% in group B (P < 0.0001). The mean duration of oesophageal acid exposure during NAB was significantly shorter in group B (18 +/- 6 min) than in group A (42 +/- 9 min, P=0.04). SUMMARY: Adding a bedtime H2-blocker to the treatment enhanced nocturnal gastric pH control and decreased NAB compared to the proton pump inhibitor b.d. regimen. A bedtime H2-blocker also decreased oesophageal acid exposure during NAB. CONCLUSION: Adding a bedtime H2-blocker to a proton pump inhibitor b.d. regimen should be considered in patients who require continued nocturnal gastric acid control whilst taking proton pump inhibitor b.d.

Anti-Ulcer Agents↗

PubMed2004

Guidelines for the appropriate use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitors in patients requiring chronic anti-inflammatory therapy.

AIM: To rationalize decision making around the use of different non-steroidal anti-inflammatory drug (NSAID) treatment strategies in patients with varying degrees of gastrointestinal and cardiovascular risk. METHODS: The panel comprised nine physicians (three rheumatologists, two internists, two gastroenterologists and two cardiologists) from geographically diverse areas practising in community-based settings (n = 4) and academic institutions (n = 5). A literature review was performed by the authors on the risks, benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitor co-therapy. The RAND/UCLA Appropriateness Method was used to rate 304 clinical scenarios as 'appropriate', 'uncertain' or 'inappropriate'. RESULTS: In patients with no previous gastrointestinal event and not concurrently on aspirin (low risk), the panel rated the use of an NSAID alone as 'appropriate' for those aged < 65 years, and the use of an NSAID +proton pump inhibitor or cyclo-oxygenase-2-specific inhibitor + proton pump inhibitor as 'inappropriate'. For patients aged > 65 years and at low risk, an NSAID or cyclo-oxygenase-2-specific inhibitor alone was rated as 'uncertain'. For patients with a previous gastrointestinal event or who concurrently received aspirin, an NSAID alone was rated as 'inappropriate', and either a cyclo-oxygenase-2-specific inhibitor or an NSAID +proton pump inhibitor was rated as 'appropriate'. Finally, for patients with a previous gastrointestinal event and on aspirin, an NSAID or cyclo-oxygenase-2-specific inhibitor in conjunction with a proton pump inhibitor was rated as 'appropriate'. CONCLUSIONS: Clinicians and managed care entities need to balance the risks, benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and the prophylactic use of proton pump inhibitors. The guidelines given here can assist this process.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

Validation of a short questionnaire in English and French for use in patients with persistent upper gastrointestinal symptoms despite proton pump inhibitor therapy: the PASS (Proton pump inhibitor Acid Suppression Symptom) test.

BACKGROUND: The management of persistent symptoms during acid suppression therapy in patients with gastroesophageal reflux disease or dyspepsia might be improved if patient-physician communication regarding the presence and character of these persistent symptoms were facilitated. AIM: To validate a short, simple questionnaire (the Proton pump inhibitor [PPI] Acid Suppression Symptom [PASS] test), in English and French, to identify patients with persistent acid-related symptoms during PPI therapy and document their response to a change in therapy. METHODS: Patients with persistent acid-related symptoms on PPI therapy were interviewed to produce a draft, five-item questionnaire; content validity was evaluated by focus groups comprising English- and French-speaking patients. Psychometric validity was subsequently evaluated in a multicentre, family practice-based study of English- and French-speaking patients with persistent acid-related upper gastrointestinal symptoms despite PPI therapy. The PASS test, Global Overall Symptom scale, Gastrointestinal Symptom Rating Scale (GSRS), Quality of Life in Reflux and Dyspepsia questionnaire and Reflux Disease Questionnaire were completed at baseline and repeated after one week while patients continued their original PPI therapy. All patients then received esomeprazole 40 mg once daily for four weeks, after which all questionnaires and an evaluation of overall treatment effect were completed. RESULTS: Content validity was established in 20 English- and 16 French-speaking patients. Psychometric validation in 158 English- and 113 French-speaking patients revealed good-to-excellent test-retest reliability coefficients: 0.76 for English; 0.68 for French. For construct validity, the PASS test showed moderate-to-high correlation with the GSRS scale (0.51 for English; 0.43 for French). After four weeks of therapy, the PASS test score fell to zero in 30% of English- and 33% of French-speaking patients, while the Global Overall Symptom score fell to one (no symptoms) in 32% of patients (English- and French-speaking); the PASS test demonstrated good responsiveness in comparison with the GSRS, Reflux Disease Questionnaire and Quality of Life in Reflux and Dyspepsia questionnaire. CONCLUSION: The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.

Dyspepsia↗