Evaluation of bioequivalence between a single-capsule formulation of esomeprazole 40 mg and acetylsalicylic acid 325 mg and the monotherapies given separately in healthy volunteers.

OBJECTIVE: The aim of this study was to investigate the bioequivalence of a single oral dose of esomeprazole 40 mg and acetylsalicylic acid 325 mg when formulated as a single capsule, relative to the components given as separate monotherapies. METHODS: This was an open, randomized, single-center, single-dose, 2-stage group sequential design, 2-way crossover study (NCT00688428) in 49 healthy adult volunteers (29 women). In each treatment period, subjects received a single dose of esomeprazole 40 mg and ASA 325 mg formulated as a single capsule or as separate monotherapies given in combination. Treatment periods were separated by a washout period of at least 6 days. The bioequivalence of a single-capsule formulation of esomeprazole 40 mg and ASA 325 mg relative to the monotherapies given individually was assessed by the geometric mean ratios of the area under the plasma concentration-time curve (AUC) and observed maximum plasma concentration (Cmax). If the 94% confidence interval (CI) of the geometric mean ratios of AUC and Cmax were within 0.80 - 1.25, bioequivalence would be established. A 94% CI was used to compensate for the multiple analyses of the study design, and to assure that the actual overall confidence level was 90%. RESULTS: The geometric mean ratios of the AUC for esomeprazole 40 mg and ASA 325 mg when administered in the single capsule formulation, relative to the monotherapies were 0.97 (94% CI, 0.90 - 1.04) and 1.04 (94% CI, 1.00 - 1.08). The corresponding mean geometric ratios for Cmax were 0.99 (94% CI, 0.90 - 1.09) and 1.02 (94% CI, 0.92 - 1.13). CONCLUSIONS: Treatment with esomeprazole 40 mg and ASA 325 mg formulated as a single capsule is bioequivalent to the separate monotherapies of esomeprazole 40 mg and ASA 325 mg when given in combination as separately-administered drugs in healthy adult subjects.

Predictors of gastroduodenal erosions in patients taking low-dose aspirin.

BACKGROUND: Gastroduodenal ulcers are common in patients taking low-dose aspirin. However, the factors predisposing to mucosal erosions, the precursor lesions, are not well known. AIMS: To examine the potential risk factors for the development of erosions in patients chronically taking low-dose aspirin. METHODS: Patients included were taking aspirin 75-325 mg daily for >28 days. Exclusion criteria included use of nonsteroidal anti-inflammatory and ulcer-healing drugs. Demographic data were collected at baseline, prior to endoscopy to determine the frequency and number of erosions and Helicobacter pylori status. In those without ulcer or other exclusions, endoscopy was repeated at 3 months. RESULTS: Fewer patients had gastric erosions if they were H. pylori +ve (48.5% vs. 66.4% in H. pylori-ve patients at baseline, P = 0.17; 40.0% vs. 64.1% at 3 months, P = 0.029). If gastric erosions were present, they were also less numerous in H. pylori +ve patients (3.61 +/- 0.83 vs. 4.90 +/- 0.53 at baseline, P = 0.026; 2.17 +/- 0.68 vs. 5.68 +/- 0.86 at 3 months, P = 0.029). There was a trend (0.1 > P > 0.05) for more gastric erosions in those taking >100 mg/day aspirin. Males had more duodenal erosions at baseline (25.2% vs. 7.5%, P = 0.016). Patient age did not affect the presence or number of erosions. H. Pylori was not significantly associated with duodenal erosion numbers. CONCLUSIONS: Helicobacter pylori infection may partially protect against low-dose aspirin-induced gastric erosions; damage to the stomach appears weakly dose-related; and older age does not increase the risk of erosions.

Evaluation of the pharmacokinetic interaction between esomeprazole (40 mg) and acetylsalicylic acid (325 mg) in healthy volunteers.

OBJECTIVE: To evaluate the effect of esomeprazole on the pharmacokinetics of low-dose acetylsalicylic acid (ASA) during repeated co-administration. METHODS: This was an open, randomized, 3-way crossover study in 55 healthy volunteers. Treatment periods comprised 5 days' oral esomeprazole (40 mg) or ASA (325 mg) alone, or in combination, separated by washout of >or= 13 days. The primary pharmacokinetic end points were steady-state area under the concentration-time curve (AUCtau) and observed maximum plasma concentration (Cmax) of ASA +/- esomeprazole. RESULTS: The estimates (90% confidence interval) of the geometric mean ratios for AUCtau and Cmax of ASA +/- esomeprazole were 1.04 (1.00 - 1.09) and 1.12 (1.03 - 1.22), respectively. Corresponding results for esomeprazole +/- ASA were 0.93 (0.89 - 0.98) and 0.96 (0.91 - 1.01), respectively. Administration of esomeprazole and ASA in combination was well tolerated. CONCLUSIONS: There was no pharmacokinetic interaction between esomeprazole (40 mg) and ASA (325 mg) during repeated co-administration in healthy volunteers.

Systematic review: ulcer definition in NSAID ulcer prevention trials.

BACKGROUND: In clinical trials of peptic ulcer prevention, the most appropriate definition of an ulcer remains challenging. AIMS: To evaluate the ulcer definitions used in clinical trials of ulcer prevention among non-steroidal anti-inflammatory drug users and to determine whether any specific definition is preferred. METHODS: A systematic literature search of the PubMed, Medline and EMBASE databases was conducted. Results were limited to full papers published in English from June 1987 to June 2007 that met the following criteria: randomized, controlled non-steroidal anti-inflammatory drug trials of > or =8 weeks' duration, with a primary end point of ulcer upon endoscopy. RESULTS: Forty five publications met the inclusion criteria and were reviewed. Overall, an ulcer diameter of > or =3 mm was used in 25 publications and most included a description of ulcer depth. Of the remainder, ulcer was defined as any lesion with unequivocal/observable depth (with no lower limit for ulcer diameter; five publications) or an excavated mucosal break >3 mm (one publication), whereas nine defined a minimum ulcer size of > or =5 or >5 mm. Ulcer definition was unclear in the remaining five publications. CONCLUSION: In clinical trials of ulcer prevention among non-steroidal anti-inflammatory drug users, a gastric or duodenal lesion > or =3 mm in diameter with significant depth is the preferred definition.

Efficacy of esomeprazole for resolution of symptoms of heartburn and acid regurgitation in continuous users of non-steroidal anti-inflammatory drugs.

BACKGROUND: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal symptoms such as heartburn and acid regurgitation. AIM: To assess the efficacy of esomeprazole 20 and 40 mg for resolution of heartburn and acid regurgitation in continuous NSAIDs. METHODS: A post hoc analysis of five clinical trials was performed. Two identically designed, placebo-controlled, 4-week studies (NASA1, SPACE1) enrolled non-ulcer, NSAIDs-treated patients with upper abdominal pain, discomfort or burning. PLUTO and VENUS were identically designed, placebo-controlled, 6-month studies that enrolled patients at risk of NSAIDs-induced ulcers. Study 285 was an 8-week comparative study with ranitidine (300 mg/day) in patients with NSAIDs-induced gastric ulcers. Resolution of investigator-assessed heartburn and acid regurgitation was defined as symptom severity of 'none' in the last 7 days. RESULTS: In NASA1/SPACE1, heartburn resolved in 61% and 62% of patients taking esomeprazole 20 and 40 mg, respectively (vs. 36% on placebo, P < 0.001), and acid regurgitation resolved in 65% and 67% (vs. 48%, P < 0.001). Resolution of both symptoms was greater with esomeprazole than with placebo in PLUTO/VENUS (P

Is ranitidine therapy sufficient for healing peptic ulcers associated with non-steroidal anti-inflammatory drug use?

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of serious gastroduodenal events. To minimise these risks, patients often require concomitant acid-suppressive therapy. We conducted a literature review of clinical trials examining use of ranitidine 150 mg twice daily to heal gastroduodenal ulcers (GU) in NSAID recipients. Seven studies were identified. After 8 weeks' treatment with ranitidine, GU healing rates ranged from 50% to 74% and rates of duodenal ulcer (DU) healing ranged from 81% to 84%. Ranitidine was more effective when NSAIDs were discontinued (healing rates reaching 95% and 100%, respectively). The ulcer healing rate with sucralfate was similar to that of ranitidine. However, proton pump inhibitor (PPI) therapy was associated with significantly greater rates of both GU and DU healing than ranitidine; 8-week GU rates were 92% and 88% with esomeprazole 40 mg and 20 mg, respectively (vs. 74% with ranitidine, p < 0.01). For omeprazole, 8-week healing rates were 87% with omeprazole 40 mg and 84% with omeprazole 20 mg (vs. 64% for ranitidine, p < 0.001), and for lansoprazole the corresponding values were 73-74% and 66-69% for the 30 mg and 15 mg doses, respectively (vs. 50-53% for ranitidine, p < 0.05). In the PPI study reporting DU healing the values were 92% for omeprazole 20 mg (vs. 81% for ranitidine, p < 0.05) and 88% for omeprazole 40 mg (p = 0.17 vs. ranitidine). NSAID-associated GU are more likely to heal when patients receive concomitant treatment with a PPI rather than ranitidine.

Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin.

BACKGROUND: Aspirin is valuable for preventing vascular events, but information about ulcer frequency is necessary to inform risk-benefit decisions in individual patients. AIM: To determine ulcer prevalence and incidence in a population representative of those given aspirin therapy and evaluate risk predictors. METHODS: Patients taking aspirin 75-325 mg daily were recruited from four countries. Exclusions included use of gastroprotectant drugs or other non-steroidal anti-inflammatory drugs. We measured point prevalence of endoscopic ulcers, after quantitating dyspeptic symptoms. Incidence was assessed 3 months later in those eligible to continue (no baseline ulcer or reason for gastroprotectants). RESULTS: In 187 patients, ulcer prevalence was 11% [95% confidence interval (CI) 6.3-15.1%]. Only 20% had dyspeptic symptoms, not significantly different from patients without ulcer. Ulcer incidence in 113 patients followed for 3 months was 7% (95% CI 2.4-11.8%). Helicobacter pylori infection increased the risk of a duodenal ulcer [odds ratio (OR) 18.5, 95% CI 2.3-149.4], as did age >70 for ulcers in stomach and duodenum combined (OR 3.3, 95% CI 1.3-8.7). CONCLUSIONS: Gastroduodenal ulcers are found in one in 10 patients taking low-dose aspirin, and most are asymptomatic; this needs considering when discussing risks/benefits with patients. Risk factors include older age and H. pylori (for duodenal ulcer).

Lack of Pharmacokinetic Interaction between Esomeprazole and the Nonsteroidal Anti-Inflammatory Drugs Naproxen and Rofecoxib in Healthy Subjects.

BACKGROUND: We investigated the potential interactions between esomeprazole and a non-selective nonsteroidal anti-inflammatory drug (NSAID; naproxen) or a cyclo-oxygenase (COX)-2-selective NSAID (rofecoxib) in healthy subjects. METHODS: Two studies of identical randomised, open, three-way crossover design were conducted. Subjects (n = 32 for both studies) were to receive 1 week's treatment with esomeprazole 40mg once daily (studies A and B), naproxen 250mg twice daily (study A), rofecoxib 12.5mg once daily (study B), and esomeprazole in combination with naproxen (study A) or rofecoxib (study B). Study periods were separated by a 2-week washout period. RESULTS: On day 7 of dosing, the ratios (and 95% CIs) for the area under the plasma concentration-time curve during the dosing interval (AUC(tau)) and observed maximum plasma concentration (C(max)) of esomeprazole and NSAID combination/NSAID alone were 0.98 (0.94, 1.01) and 1.00 (0.97, 1.04), respectively, for study A, and 1.15 (1.06, 1.24) and 1.14 (1.02, 1.28), respectively, for study B. The ratios (and 95% CIs) for AUC(tau) and C(max) of esomeprazole and NSAID combination/esomeprazole alone were 0.96 (0.89, 1.03) and 0.92 (0.85, 1.00), respectively, for study A, and 1.05 (0.96, 1.15) and 1.05 (0.94, 1.18), respectively, for study B. All treatments were well tolerated during the study period. CONCLUSION: Naproxen and rofecoxib do not interact with esomeprazole, and esomeprazole does not affect the pharmacokinetics of naproxen or rofecoxib. These findings indicate that esomeprazole can be used in combination with NSAIDs without the risk of a pharmacokinetic interaction.

The Visceral Sensitivity Index: development and validation of a gastrointestinal symptom-specific anxiety scale.

BACKGROUND: Anxiety related to gastrointestinal sensations, symptoms or the contexts in which these may occur is thought to play a significant role in the pathophysiology as well as in the health outcomes of patients with irritable bowel syndrome. AIM: To develop a valid and reliable psychometric instrument that measures gastrointestinal symptom-specific anxiety. METHODS: External and internal expert panels as well as a patient focus group evaluated a large pool of potential item stems gathered from the psychological and gastrointestinal literature. Potential scale items were then administered to 96 patients diagnosed with irritable bowel syndrome along with a set of validating questionnaires. Final item selection was based upon rigorous empirical criteria and the psychometric properties of the final scale were examined. RESULTS: A final unidimensional 15-item scale, the Visceral Sensitivity Index, demonstrated excellent reliability as well as good content, convergent, divergent and predictive validity. CONCLUSIONS: The findings suggest that the Visceral Sensitivity Index is a reliable, valid measure of gastrointestinal symptom-specific anxiety that may be useful for clinical assessment, treatment outcome studies, and mechanistic studies of the role of symptom-related anxiety in patients with irritable bowel syndrome.

An irritable bowel syndrome-specific symptom questionnaire: development and validation.

BACKGROUND: No self-assessment instruments are available to assess symptoms of irritable bowel syndrome (IBS). Our aim was to develop a disease-specific symptom questionnaire for use in patients with IBS. METHODS: Two-hundred-and-thirty-four patients (77% F) with a mean age of 44 years took part in a psychometric evaluation using the previously validated Gastrointestinal Symptom Rating Scale modified for use in patients with IBS (GSRS-IBS). This version was tested against several disease-specific health-related quality of life (HRQL) questionnaires. Items with a high ceiling effect, items that measured a different construct, and items showing high correlation (>0.80) to another item were removed. A confirmatory factor analysis was also performed. RESULTS: The final questionnaire included 13 items depicting problems with satiety, abdominal pain, diarrhoea, constipation and bloating. The internal consistency reliability was high, ranging from 0.74 (pain) to 0.85 (satiety). The associations between similar constructs in the GSRS-IBS and the various HRQL scores confirmed the construct validity. Pain, bloating and diarrhoea were the symptom clusters that impaired HRQL the most. CONCLUSION: The GSRS-IBS is a short and user-friendly instrument with excellent psychometric properties.

Randomized, double-blind, placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome.

BACKGROUND: Post-infectious irritable bowel syndrome is associated with increased serotonin-containing enterochromaffin cells and lymphocytes in rectal biopsies. Animal studies have suggested that steroids reduce the lymphocyte response and suppress some of the post-infectious changes in neuromuscular function. AIM: To evaluate whether steroids reduce the number of enterochromaffin cells and improve the symptoms of post-infectious irritable bowel syndrome. METHODS: Twenty-nine patients with post-infectious irritable bowel syndrome underwent a randomized, double-blind, placebo-controlled trial of 3 weeks of oral prednisolone, 30 mg/day. Mucosal enterochromaffin cells, T lymphocytes and mast cells were assessed in rectal biopsies before and after treatment, and bowel symptoms were recorded in a daily diary. RESULTS: Initial enterochromaffin cell counts were increased and correlated with initial lamina propria T-lymphocyte counts (r = 0.460, P = 0.014). Enterochromaffin cell counts did not change significantly after either prednisolone (- 0.8% +/- 9.2%) or placebo (7.9% +/- 7.9%) (P = 0.5). Although lamina propria T-lymphocyte counts decreased significantly after prednisolone (22.0% +/- 5.6%, P = 0.003), but not after placebo (11.5% +/- 8.6%, P = 0.1), this was not associated with any significant treatment-related improvement in abdominal pain, diarrhoea, frequency or urgency. CONCLUSIONS: Prednisolone does not appear to reduce the number of enterochromaffin cells or cause an improvement in symptoms in post-infectious irritable bowel syndrome. Other approaches to this persistent condition are indicated.

Relative contribution of mucosal injury and Helicobacter pylori in the development of gastroduodenal lesions in patients taking non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIMS: A past history of peptic ulceration increases the risk of an ulcer developing during non-steroidal anti-inflammatory drug (NSAID) use. Whether this is due to Helicobacter pylori infection or to reactivation of the original lesion is unclear. METHODS: We used multivariate regression analyses of three large similar trials to identify factors that placed patients at high risk of ulcer development or relapse. We compared the efficacy of omeprazole 20 mg daily, misoprostol 200 micro g twice daily, and ranitidine 150 mg twice daily in preventing ulcers and erosions at different sites and in patients who were H pylori positive and negative. RESULTS: Patients with endoscopic lesions (which healed) initially were significantly more likely than those without to develop further erosions or ulcers during treatment (rate ratio 2.12, 1.07-4.17). Risk mounted further with ulcers versus erosions, particularly those that had been slow to heal. There was a highly significant tendency for the relapse lesion to replicate the site and type of the original lesion (mean odds ratios ranging from 3 to 14). Treatment failure was significantly less likely with omeprazole than with placebo, misoprostol, or ranitidine. This advantage was especially evident in H pylori positive patients receiving acid suppression (5.7% v 16.6% for gastric ulcer with omeprazole). CONCLUSIONS: Relapse of lesions in patients taking NSAIDs was highly site and type specific and not adversely affected by H pylori status. This strongly implies that local mucosal factors predispose to ulcer development in patients taking NSAIDs. Identification of the responsible mucosal changes would aid understanding and could promote better treatment.

Influence of sex and Helicobacter pylori on development and healing of gastroduodenal lesions in non-steroidal anti-inflammatory drug users.

BACKGROUND AND AIMS: Factors predisposing to endoscopic ulcer formation or healing with non-steroidal anti-inflammatory drugs (NSAIDs) have not been well defined. METHODS: We used multivariate analysis of data from three large similar trials to identify factors associated with endoscopic lesions and healing. We compared the effectiveness of omeprazole 20 mg and 40 mg daily, misoprostol 200 micro g four times daily, and ranitidine 150 mg twice daily in healing ulcers and erosions at different sites and in patients who were Helicobacter pylori positive and negative. RESULTS: Older age, past ulcer history, rheumatoid arthritis, and H pylori infection were significantly associated with ulcers. Duodenal ulcer was significantly more likely than gastric ulcer with a past ulcer history (odds ratio 1.59, 1.16-2.17), H pylori infection (1.4, 1.04-1.92), and male sex (2.35, 1.75-3.16) while female sex, older age (> or = 60 years: 1.39, 1.03-1.88), and higher NSAID dose (>1 defined daily dose: 1.57, 1.16-2.14) were associated with gastric ulceration. Sex differences were seen in both H pylori positive and negative patients. Gastric and duodenal ulcer healing was significantly faster with omeprazole 20 mg than with misoprostol 200 micro g four times daily or ranitidine 150 mg twice daily although misoprostol was more effective at healing erosions. Gastric ulcer healing was slower with large ulcers (0.37, 0.25-0.54 for >10 mm v 5-10 mm) or a past ulcer history (0.51, 0.34-0.76), and faster with H pylori infection (1.55, 1.06-2.29), especially with acid suppression (72% v 37% at four weeks with ranitidine). CONCLUSIONS: Among NSAID users, H pylori and male sex independently increase the likelihood of duodenal ulceration. H pylori infection does not affect duodenal ulcer healing and enhances gastric ulcer healing by ranitidine and possibly other acid suppressing treatments.

Gastro-duodenal protection in an era of cyclo-oxygenase-2-selective nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective and necessary for the relief of pain and inflammation in patients with arthritis. NSAIDs are however also associated with an increased risk for ulceration in the stomach and in the duodenum, and many NSAID users experience bothersome dyspeptic symptoms during continued NSAID therapy. PPIs like omeprazole, have been shown to heal and to prevent ulcers and dyspeptic symptoms during continued NSAID therapy, and during continued NSAID therapy the prostaglandin analogue, misoprostol, has been shown to reduce the risk for ulcer complications. The COX-2 selective NSAID, rofecoxib, is in comparison with naproxen, a non-selective NSAID, associated with fewer clinically important upper gastrointestinal events. The incidence of myocardial infarctions seems, however, to be lower with naproxen than with rofecoxib, and this is expected to lead to low-dose aspirin use in rofecoxib users at risk for cardiovascular events. Co-administration of the COX-2 selective NSAID, celecoxib, and low-dose aspirin, is associated with the same risk for upper gastrointestinal ulcer complications alone and combined with symptomatic ulcers, as the non-selective NSAIDs, ibuprofen and diclofenac. A proton pump inhibitor (PPI) should be used for healing of NSAID-associated ulcers, and a PPI or misoprostol should be considered for prevention of ulceration in non-selective NSAID users at risk for ulceration. The experience with COX-2 selective NSAIDs is still limited, and it remains to be studied whether subpopulations of COX-2 selective NSAID users will benefit from gastro-duodenal protection.

A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced?

BACKGROUND: Dyspepsia is a common symptom for which an organic cause is found in only 40% of patients. When no cause is apparent and the dyspepsia is considered to be idiopathic, a diagnosis of non-ulcer dyspepsia is made. The pathophysiology of non-ulcer dyspepsia is poorly understood and numerous theories have been put forward, including a theory of enhanced central serotoninergic receptor sensitivity. AIM: To determine the sensitivity of serotonin receptors in non-ulcer dyspepsia. METHODS: Using a randomized, double-blind, placebo-controlled design, we compared buspirone (a serotonin type 1a partial agonist)-stimulated prolactin release in 50 patients and 59 healthy comparison subjects. Buspirone, 30 mg, or matching placebo was administered on two separate occasions and prolactin release over 180 min was monitored. Patients and healthy subjects received both treatments in random order, 1 week apart. RESULTS: Overall, patients with non-ulcer dyspepsia had greater prolactin release in response to the buspirone challenge than the healthy comparison subjects, with differences most significant at 90 min following the challenge. Enhancement occurred in patients both with and without Helicobacter pylori infection. Female subjects, both patients and healthy volunteers, showed a greater response to buspirone than male subjects, and the augmentation of response observed in male and female patients was greater in females. CONCLUSIONS: Patients with non-ulcer dyspepsia have enhanced central serotoninergic responses and such responses are independent of H. pylori infection. Blockade of such receptors might be an appropriate therapeutic strategy.

Impact of cortisol on buspirone stimulated prolactin release: a double-blind placebo-controlled study.

Buspirone is known to stimulate prolactin release. Clinical studies (e.g. in chronic fatigue syndrome) suggest that the response may be influenced by baseline cortisol levels. We conducted a double-blind placebo-controlled study to examine the relationship between the prolactin response to buspirone challenge and baseline cortisol level. Fifty healthy volunteers took part in the study. Buspirone was found to consistently elevate PRL levels above those seen following placebo administration. The PRL response as measured by area under the curve was highly correlated with the baseline cortisol level.

Characteristics of patients with irritable bowel syndrome recruited from three sources: implications for clinical trials.

BACKGROUND: Variation in the characteristics of irritable bowel syndrome patients recruited for clinical trials from different sources could affect their response and the generalizability of trial results. AIM: To describe and compare the characteristics of three different groups of irritable bowel syndrome patients recruited into a 'mock clinical trial.' METHODS: We enrolled 245 irritable bowel syndrome patients from three sources: (i) 121 from British primary practitioners; (ii) 72 from California newspaper advertisements; and (iii) 52 from a California gastroenterologist's practice. We obtained demographic, clinical, and Hospital Anxiety and Depression (HAD) Scale data. RESULTS: Most patients were young to middle-aged women; the majority reported symptoms for > 5 years in all three groups. Subject characteristics varied among the groups. Typically, primary care patients were anxious, smokers and daily alcohol drinkers who had sought care recently for irritable bowel syndrome and tried antispasmodic drugs. Their symptoms were intermediate in severity between those of the other two groups. Advertisement subjects were the oldest, most highly educated, most often depressed, and were least likely to have sought care recently for symptoms, which were almost uniformly only moderate in severity. Gastroenterologist patients tended to be anxious and had nearly all sought care recently for symptoms, which were the most severe and most likely to include all three pain-related Rome I criteria. CONCLUSION: Recruitment methodology affects important characteristics of an irritable bowel syndrome study group.

Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misoprostol.

OBJECTIVE: To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions. METHODS: Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months). RESULTS: Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea. CONCLUSION: QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.

Lack of drug-drug interaction between three different non-steroidal anti-inflammatory drugs and omeprazole.

OBJECTIVE: To study, in three separate investigations, the potential interaction between omeprazole and three different non-steroidal anti-inflammatory drugs (NSAIDs; diclofenac, naproxen and piroxicam) in healthy male and female subjects. METHODS: Each investigation was an open, randomized, three-way cross-over study, in which the subjects were given omeprazole 20 mg once daily for 1 week, the NSAID in therapeutic daily doses (diclofenac 50 mg bid, naproxen 250 mg bid, or piroxicam 10 mg om), or a combination of omeprazole and each NSAID. The plasma concentrations of the NSAID as well as of omeprazole were determined on the last day of each investigation period. RESULTS: None of the NSAIDs studied had any effect on the plasma concentration versus time curve (AUC) of omeprazole. It was also demonstrated that omeprazole 20 mg daily had no significant influence on the pharmacokinetics of the NSAIDs. The AUC ratio, (NSAID +omeprazole):NSAID alone, was 1.11, 0.99, and 0.99 for diclofenac, naproxen, and piroxicam, respectively. CONCLUSION: Diclofenac, naproxen, and piroxicam can be administered together with omeprazole 20 mg daily without need for dosage alteration. There was no significant change in the bioavailability of theses NSAIDs during omeprazole therapy in this study.

Omeprazole and H2-receptor antagonists in the acute treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis: a meta-analysis.

This paper is a meta-analysis of 30 published, double-blind clinical trials comparing omeprazole with ranitidine or cimetidine for the treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. These studies compare the recommended doses of omeprazole with those for ranitidine and cimetidine, and the confidence intervals for the therapeutic gain show that the findings are highly reliable. The difference in healing rates favoured omeprazole over ranitidine in patients with duodenal ulcer after 2 weeks of treatment (15.2 percentage units; P < 0.001), and after 4 weeks of treatment in patients with gastric ulcer (9.9 percentage units; P = 0.005), or reflux oesophagitis (23 percentage units; P < 0.001). Similarly, omeprazole gave a 20.6 percentage units higher average healing rate than cimetidine in patients with duodenal ulcer after 2 weeks of treatment (P < 0.0001). Significantly more patients treated with omeprazole were free of symptoms at their first follow-up visit than patients treated with ranitidine or cimetidine.