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.

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.

Does esomeprazole prevent post-operative nausea and vomiting?

BACKGROUND: Esomeprazole is a potent proton pump inhibitor (PPI), reducing acid production as well as gastric juice volume. This study evaluated the possible beneficial effect of esomeprazole on reducing post-operative nausea and vomiting (PONV). METHODS: Patients undergoing laparoscopic or open gynaecological surgery, or laparoscopic cholecystectomy were randomized to receive three peri-operative doses double blindly of either esomeprazole 40 mg or placebo, given intravenously or orally. All patients were given a standardized anaesthesia regimen including fentanyl and sevoflurane/nitrous oxide. RESULTS: The study population consisted of 284 patients. Demographic data and known PONV risk factors were similar for the two treatment groups. PONV was observed in 77% of patients on esomeprazole vs. 81% on placebo (NS) and rescue antiemetic medication was needed in 56% vs. 53%, respectively (NS). The proportion of patients that vomited during 0-24 h was lower on esomeprazole than placebo (38% vs. 49%; NS), and the mean amount of vomit was significantly lower (52 vs. 86 g; P < 0.05). The use of neostigmine, use of opioids and type of surgery were significant risk factors for PONV (P < 0.05). The 24-h incidence of PONV was 63% after laparoscopic gynaecology, 80% after laparoscopic cholecystectomy and 88% after open gynaecological laparotomy, whereas laparoscopic cholecystectomy had the lowest risk when corrected for other risk factors of PONV. CONCLUSION: Esomeprazole had no clinically relevant effect on the overall 24-h incidence of PONV. However, esomeprazole significantly reduced the total amount of vomit during 24-h post-operatively. This may be of value in patients with an increased risk of pulmonary aspiration.

Histological effects of esomeprazole therapy on the squamous epithelium of the distal oesophagus.

BACKGROUND: Proton pump inhibitor therapy has been reported to reduce proliferative changes of the oesophagus significantly in gastro-oesophageal reflux disease (GERD). AIM: To assess the histological effects of esomeprazole treatment on the oesophagus. METHODS: Data were derived from a subgroup of patients participating in the proGERD study, who had either erosive reflux disease (n = 720) or non-erosive reflux disease (n = 35) and who had biopsy data from two sites [(i) 2 cm above the z-line and (ii) at the z-line], obtained at baseline and following treatment with esomeprazole. Proliferative changes of the squamous epithelium were assessed histologically by measuring thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness. RESULTS: In erosive reflux disease patients, the thickness of the basal cell layer and length of the papillae pretreatment were associated with the severity of oesophagitis (P < 0.05), at both biopsy sites. After esomeprazole treatment, baseline thickness and length of papillae were significantly reduced (P < 0.05) at both biopsy sites in non-erosive reflux disease and erosive reflux disease patients (particularly those with Los Angeles grades C and D). CONCLUSION: This demonstrates a strong correlation between severity of GERD and histological parameters. Esomeprazole therapy resulted in clear reversal of proliferative changes observed prior to treatment in the squamous epithelium at both biopsy locations.

Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study.

BACKGROUND: Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse. AIM: To compare endoscopic and symptomatic remission rates over 6 months' maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis. METHODS: Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study. RESULTS: A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro-oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001). CONCLUSIONS: Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease symptoms.

A randomized comparative study of esomeprazole 40 mg versus pantoprazole 40 mg for healing erosive oesophagitis: the EXPO study.

AIM: To assess the efficacy of the 8-week therapy with esomeprazole 40 mg vs. pantoprazole 40 mg for healing erosive oesophagitis (EE) as part of a management study. METHODS: Patients had a history of gastro-oesophageal reflux disease symptoms (> or =6 months) and had suffered heartburn on at least 4 of the 7 days preceding enrollment. Endoscopies were performed to grade EE severity using the Los Angeles (LA) classification system at baseline, 4 and 8 weeks (if unhealed at 4 weeks). Heartburn severity was recorded by patients on diary cards. The primary end point was healing of EE by week 8 of treatment. RESULTS: Of 3170 patients randomized, the intent-to-treat population consisted of 3151 patients (63% male, mean age: 50.6 years, 27% Helicobacter pylori-positive). Esomeprazole 40 mg healed a significantly greater proportion of EE patients than pantoprazole 40 mg at both 4 weeks (life table estimates: esomeprazole 81%, pantoprazole 75%, P < 0.001) and 8 weeks (life table estimates: esomeprazole 96%, pantoprazole 92%, P < 0.001). The median time to reach sustained heartburn resolution was 6 days in patients receiving esomeprazole and 8 days with pantoprazole (P < 0.001). CONCLUSION: Esomeprazole 40 mg is more effective than pantoprazole 40 mg for healing EE and providing resolution of associated heartburn.

What parameters are relevant for the histological diagnosis of gastroesophageal reflux disease without Barrett's mucosa?

BACKGROUND/AIMS: There are still ongoing controversies as to which histological parameters allow the diagnosis of gastroesophageal reflux disease (GERD). The aim of the present analysis was to relate histological changes of the esophageal squamous epithelium to different severities of GERD. METHODS: Data were obtained from patients participating in the ProGERD study, who had either erosive reflux disease (ERD, n = 3,245) or non-erosive reflux disease (NERD, n = 2,970). 1,475 patients fulfilled our requirement of having complete biopsy data from two sites (2 cm above the z-line and at the z-line). Changes in the squamous epithelium were assessed by measuring the thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness and counting interepithelial inflammatory cells. RESULTS: The most useful parameters for histological assessment of GERD (given as means, 2 cm above the z-line and at the z-line, respectively) were elongation of the papillae: NERD 40.7 and 48.9%; ERD 46.1 and 54.9% and basal cell hyperplasia: NERD 12.7 and 17.9%; ERD 15.7 and 23.0%. The occurrence of intraepithelial lymphocytic infiltrates, however, is dependent on the severity of GERD, and they are more common than neutrophilic and eosinophilic granulocytes. CONCLUSION: This study shows that both NERD and ERD can be diagnosed histologically if biopsies are obtained from the distal esophagus or from the z-line. Intraepithelial inflammatory cells are rare and show a high specificity, but very low sensitivity.