A comparison of esomeprazole and lansoprazole for control of intragastric pH in patients with symptoms of gastro-oesophageal reflux disease

BACKGROUND: Intragastric acid suppression is the most direct measure of the pharmacodynamic efficacy of proton pump inhibitors, which are the most effective drugs for acid-related diseases. AIM: To compare the effectiveness of once and twice daily dosing of lansoprazole and esomeprazole in controlling intragastric acidity (target gastric pH > 4.0) over a 24-hour period. METHODS: In an open-label, two-way crossover study, 45 Helicobacter pylori-negative patients with gastro-oesophageal reflux disease were randomized to receive one of two regimens: 30 mg lansoprazole or esomeprazole 40 mg once daily. Intragastric pH was assessed by 24-hour pH monitoring on day 5 of each regimen. Dosing was increased to twice daily and pH was reassessed on day 10. Following a 14-day washout, patients were crossed over to the other medication and the dosage regimens and pH assessments were repeated. RESULTS: Data were analysed from 35 patients who completed all scheduled assessments and had 24-hour monitoring for each end-point. Mean time pH > 4.0 and mean 24-hour pH were highest for esomeprazole 40 mg twice daily, followed by lansoprazole 30 mg twice daily, esomeprazole 40 mg once daily and lansoprazole 30 mg once daily. Esomeprazole 40 mg twice daily provided superior control of intragastric pH compared with either once or twice daily dosing of lansoprazole and once daily dosing of esomeprazole (P < 0.01). Esomeprazole 40 mg once daily was comparable with lansoprazole 30 mg twice daily and both were superior to lansoprazole 30 mg once daily (P < 0.01). CONCLUSIONS: Response to acid suppression treatment depends on the treatment selected. Esomeprazole 40 mg twice daily provided better control of intragastric pH than all other regimens evaluated. Esomeprazole 40 mg daily, however, was comparable with lansoprazole 30 mg twice daily and superior to lansoprazole 30 mg once daily.     

Combined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24-h intragastric pH in healthy volunteers

AIM: To compare antisecretory effects of rabeprazole and esomeprazole after single and repeat dosing in Helicobacter pylori-negative healthy volunteers. METHODS: Results were pooled from three smaller, open, crossover, randomized studies to obtain data from 80 subjects. The studies compared: (a) 5 days' dosing of 20 mg rabeprazole and esomeprazole (n = 24); (b) single doses of rabeprazole 20 mg and esomeprazole 40 mg (n = 27) and (c) 5 days' dosing of rabeprazole 10 mg and esomeprazole 20 mg (n = 29). Washout periods were > or =14 days. Intragastric pH was recorded continuously for 24 h on days 0, 1 and 5. RESULTS: Single doses of rabeprazole 20 mg maintained 24-h intragastric pH >4 for longer than esomeprazole 20 mg (45% vs. 32%; P < 0.001); rabeprazole 20 mg and esomeprazole 40 mg were equivalent in their effects. After 5 days' dosing, rabeprazole 20 mg maintained pH >4 for longer than esomeprazole 20 mg (62% vs. 56%; P = 0.046); the reverse was true for esomeprazole 20 mg vs. rabeprazole 10 mg (56% vs. 48%; P = 0.035). In general, intragastric pH AUC during 0-5 h after dosing was higher after esomeprazole than rabeprazole, whereas the reverse was true during the night. CONCLUSIONS: The order of effects on 24-h pH was: rabeprazole 10 mg < or = esomeprazole 20 mg < rabeprazole 20 mg = esomeprazole 40 mg. Esomeprazole acts faster, whereas rabeprazole's effect lasts longer.     

Esomeprazole 40 mg provides more effective intragastric acid control than lansoprazole 30 mg,omeprazole 20 mg,pantoprazole 40 mg and rabeprazole 20 mg in patients with gastro-oesophageal reflux symptoms

Objective To compare the effect of esomeprazole 40 mg with lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg on intragastric pH during single and repeated dosing in four separate studies in patients with symptoms of gastro-oesophageal reflux disorder (GERD).Methods In four randomised crossover studies, patients with symptoms of GERD received once-daily treatment with esomeprazole 40 mg or lansoprazole 30 mg (study A), omeprazole 20 mg (study B), pantoprazole 40 mg (study C) and rabeprazole 20 mg (study D) for 5 days. Continuous 24-h intragastric pH recording was performed on days 1 (except study B) and 5. Percentage of time over 24 h with intragastric pH greater than 4, 24-h median pH and the proportion of patients with pH greater than 4 for greater than or equal to 12 h and 16 h during the 24-h recording periods were investigated.Results In all four studies, esomeprazole 40 mg OD maintained intragastric pH greater than 4 for a significantly higher mean percentage of the 24-h period compared with all other proton pump inhibitors (PPIs) on days 1 (esomeprazole 40.6% versus lansoprazole 33.4%, P=0.0182; esomeprazole 50.3% versus pantoprazole 29.1%, P<0.001; esomeprazole 41.0% versus rabeprazole 29.4%, P=0.002) and 5 (esomeprazole 57.7% versus lansoprazole 44.5%, P<0.0001; esomeprazole 69.8% versus omeprazole 43.7%, P<0.0001; esomeprazole 67.0% versus pantoprazole 44.8%, P<0.001; esomeprazole 59.4% versus rabeprazole 44.5%, P<0.0001). Higher 24-h median pH and a higher proportion of patients with intragastric pH greater than 4 for greater than or equal to 12 h and 16 h were reported with esomeprazole 40 mg OD than with all the other PPIs in each study.Conclusion Esomeprazole 40 mg provides greater acid control in more patients and maintains intragastric pH greater than 4 for a longer period than lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg in patients with symptoms of GERD.The experiments within this paper comply with the current laws of the countries in which they were conducted.     

Intragastric acidity during treatment with esomeprazole 40 mg twice daily or pantoprazole 40 mg twice daily--a randomized, two-way crossover study

BACKGROUND: Patients with severe or complicated reflux disease may require higher than standard doses of a proton pump inhibitor for sufficient acid suppression. AIM: To test the hypothesis that esomeprazole 40 mg twice daily is superior to pantoprazole 40 mg twice daily in lowering intragastric acidity. METHODS: In a randomized, single-blinded, two-way crossover study, healthy subjects received esomeprazole 40 mg twice daily or pantoprazole 40 mg twice daily orally for five consecutive days. Continuous ambulatory 24-h intragastric pH was recorded on day 5 of each treatment. RESULTS: Thirty subjects were analysed. Esomeprazole provided significantly higher intragastric pH-values over the 24-h period [median intragastric pH 6.4 for esomeprazole and 5.1 for pantoprazole (P < 0.00005)]. Intragastric pH > 4 was maintained for 21.1 h with esomeprazole and 16.8 h with pantoprazole (P < 0.0001). An intragastric pH > 4 for more than 16 h was achieved in 96.7 and 56.7% of subjects, respectively (P = 0.0002). During night-time the proportion of time with intragastric pH > 4 was 85.4% with esomeprazole and 63.6% with pantoprazole (P = 0.0001). Nocturnal acid break through occurred less frequently on esomeprazole. CONCLUSIONS: Esomeprazole 40 mg twice daily provides better and more consistent intragastric acid control than pantoprazole 40 mg twice daily.     

Intragastric acid suppression and pharmacokinetics of twice-daily esomeprazole: a randomized, three-way crossover study

BACKGROUND: Patients with refractory gastro-oesophageal reflux disease, extra-oesophageal reflux symptoms, Barrett's oesophagus, or Zollinger-Ellison syndrome may require greater acid suppression than that obtained with once-daily esomeprazole. AIM: To assess gastric acid suppression (determined by intragastric pH) and pharmacokinetics of twice-daily vs. once-daily esomeprazole. METHODS: In a randomized, double-blind, three-way crossover study, healthy subjects received esomeprazole 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for five consecutive days. Twenty-four-hour continuous ambulatory intragastric pH was recorded on day 5. RESULTS: Esomeprazole 40 mg twice daily provided a mean of 19.2 h with intragastric pH > 4.0 (80.1% of a 24-h time period; 95% confidence interval 74.5-85.7%) vs. 14.2 h with 40 mg once daily (59.2%; 95% CI 53.7-64.7%) and 17.5 h with 20 mg twice daily (73.0%; 95% confidence interval 67.4-78.5%) in 25 subjects. Intragastric pH was maintained >4.0 for a similar percentage of time during active and sleeping periods for all doses. CONCLUSIONS: Esomeprazole 40 mg twice daily provides significantly greater acid suppression (number of hours in a 24-h period with pH > 4.0) than once-daily dosing and may be a reasonable consideration for patients requiring greater acid suppression for acid-related disease.     

Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators

BACKGROUND: The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid-related disease. METHODS: 1960 patients with endoscopy-confirmed reflux oesophagitis (RO) were randomized to once daily esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double-blind trial. The primary efficacy variable was the proportion of patients healed at week 8. Secondary variables included healing and heartburn resolution at week 4, time to first resolution and sustained resolution of heartburn, and per cent of heartburn-free days and nights. Safety and tolerability were also evaluated. RESULTS: Significantly more patients were healed at week 8 with esomeprazole 40 mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life table estimates, ITT analysis (each P < 0.05). Esomeprazole 40 mg was also significantly more effective than omeprazole for healing at week 4 and for all secondary variables evaluating heartburn resolution. The most common adverse events in all treatment groups were headache, abdominal pain and diarrhoea. CONCLUSION: Esomeprazole was more effective than omeprazole in healing and symptom resolution in GERD patients with reflux oesophagitis, and had a tolerability profile comparable to that of omeprazole.     

Esomeprazole

Esomeprazole, a new proton pump inhibitor, is the S-isomer of omeprazole and is the first such inhibitor to be developed as a single isomer. Esomeprazole provided better control of intragastric pH than omeprazole, lansoprazole and pantoprazole in trials conducted in patients with gastro-oesophageal reflux disease (GORD) or healthy volunteers (n = 20 to 115). In 2 large randomised, double-blind multicentre trials esomeprazole 20 and/or 40mg for 8 weeks produced higher healing rates of erosive oesophagitis and better symptom control than omeprazole 20 mg in patients with GORD. Esomeprazole 10, 20 or 40mg once daily for 6 months maintained healing versus placebo (p < 0.001) in patients with endoscopically confirmed healed erosive oesophagitis in 2 large randomised, double-blind multicentre trials. Similarly, symptom-driven on-demand use of esomeprazole effectively controlled symptoms of GORD (heartburn) for 6 months in 2 large placebo-controlled trials. Esomeprazole-based triple therapy for 7 days was as effective for eradication of Helicobacter pylori as longer omeprazole-based therapy in 2 randomised double-blind trials including about 450 patients each. Endoscopically confirmed ulcer healing 4 weeks after treatment initiation was reported in about 90% of patients with active duodenal ulcer in both treatment groups. Esomeprazole-based triple therapy for 10 days was more effective than esomeprazole plus clarithromycin for eradication of H. pylori in 233 patients.     

Pharmacokinetics and pharmacodynamics of esomeprazole, the S-isomer of omeprazole

BACKGROUND: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid-related diseases. AIM: To examine the pharmacokinetics and pharmacodynamics of esomeprazole. METHODS: In a crossover study, 12 healthy males received 5, 10 or 20 mg of esomeprazole, or 20 mg of omeprazole, once daily over 5 days. The pharmacokinetics and effects on pentagastrin-stimulated peak acid output of esomeprazole and omeprazole were studied on days 1 and 5. RESULTS: The area under the curve (AUC) of both esomeprazole and omeprazole increased from day 1 to day 5. The correlation between acid inhibition and AUC for esomeprazole could be well described with a sigmoid Emax model. The mean inhibition values of the pentagastrin-stimulated peak acid output on day 1 for 5, 10 and 20 mg of esomeprazole were 15%, 29% and 46%, respectively; the corresponding day 5 values were 28%, 62% and 90%. The mean inhibition values of the pentagastrin-stimulated peak acid output for omeprazole were 35% (day 1) to 79% (day 5). CONCLUSIONS: The pharmacokinetics of esomeprazole are time and dose dependent. There was a good correlation between AUC and effect for esomeprazole. These data suggest an increased acid inhibitory effect of esomeprazole compared to omeprazole.     

Esomeprazole: a review of its use in the management of acid-related disorders

Esomeprazole (S-isomer of omeprazole), the first single optical isomer proton pump inhibitor, generally provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In a large well designed 8-week trial in patients (n >5000) with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving lansoprazole. Respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Overall, esomeprazole was also better than omeprazole, although these differences were not always statistically significance. Ninety-two to 94% of esomeprazole recipients (40mg once daily) achieved healed oesophagitis versus 84 to 90% of omeprazole recipients (20mg once daily). Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. Resolution of heartburn was also significantly better with esomeprazole 40mg than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healing in these patients. Once-daily esomeprazole 20 or 40mg for 4 weeks resolved symptoms in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Symptoms were effectively managed in the long-term with symptom-driven on-demand esomeprazole (20 or 40mg once daily). Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Seven days' treatment (twice-daily esomeprazole 20mg plus amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in >/=86% of patients (intention-to-treat), a rate that was similar to equivalent omeprazole-based regimens. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents, with a tolerability profile similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients), with very few (<1%) drug-related serious adverse events reported. CONCLUSIONS: Esomeprazole is an effective, well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis and overall, provided better efficacy than omeprazole. Notably, in a large (n >5000 patients) double-blind trial, esomeprazole 40mg provided significantly better efficacy than lansoprazole in terms of healing rates and resolution of symptoms. Long-term therapy with esomeprazole maintained healed oesophagitis in these patients. Esomeprazole also proved beneficial in patients with symptomatic GORD without oesophagitis. Thus, esomeprazole has emerged as an option for first-line therapy in the management of acid-related disorders.     

Esomeprazole: a review of its use in the management of acid-related disorders in the US

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as a single optical isomer. It provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In large well designed 8-week trials in patients with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving omeprazole or lansoprazole. Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as the baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. In two trials, 94% of patients receiving esomeprazole 40mg once daily achieved healed oesophagitis versus 84 to 87% of omeprazole recipients (20mg once daily). In a study in >5000 patients, respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Resolution of heartburn was also significantly better with esomeprazole than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole 20 or 40mg once daily for 4 weeks proved effective in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Ten days' triple therapy (esomeprazole 40mg once daily, plus twice-daily amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in 77 to 78% of patients (intention-to-treat) with endoscopically confirmed duodenal ulcer disease. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents. The tolerability profile is similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients) and very few (<1%) drug-related serious adverse events were reported. CONCLUSIONS: Esomeprazole is an effective and well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole effectively healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis. Notably, in large (n >1900 patients) double-blind trials, esomeprazole provided significantly better efficacy than omeprazole or lansoprazole in terms of both healing rates and resolution of symptoms. Long-term therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole was also effective in patients with symptomatic GORD. Thus, esomeprazole has emerged as an effective option for first-line therapy in the management of acid-related disorders.     

Pharmacokinetic studies with esomeprazole, the (S)-isomer of omeprazole

This article reviews the pharmacokinetics of esomeprazole, the (S)-isomer of the proton pump inhibitor (PPI) omeprazole. Esomeprazole is the first single isomer PPI developed for the treatment of patients with acid-related diseases. In vitro experiments in human liver microsomes demonstrated that the formation of the hydroxy and 5-O-desmethyl metabolites of esomeprazole is via cytochrome P450 (CYP) 2C19, whereas that of the sulphone metabolite is via CYP3A4. The formation rate of the hydroxy metabolite from esomeprazole is lower than for (R)-omeprazole, but that of the 2 other metabolites is higher, demonstrating stereoselective metabolism. The sum of the intrinsic clearances of all 3 metabo- lites for esomeprazole was one-third of that for (R)-omeprazole, suggesting lower clearance of esomeprazole in vivo. In vivo investigations demonstrated that esomeprazole is chirally stable after administration. Esomeprazole is 97% bound to plasma proteins. In normal (extensive) metabolisers with regard to CYP2C19, esomeprazole is metabolised more slowly than omeprazole, resulting in a higher area under the concentration-time curve (AUC) after administration of the same dose. This is more pronounced after repeated administration rather than after a single dose. In poor metabolisers, the AUC is lower for esomeprazole than for omeprazole, contributing to less overall interindividual variability for esomeprazole than for omeprazole. In general, esomeprazole and omeprazole are subject to the same metabolic transformations. Almost complete recoveries were reported and the ratio between urinary and faecal excretion is about 4:1 for both compounds. The dose-dependent increase in AUC of esomeprazole with repeated administration results from a combination of decreased first-pass elimination and decreased systemic clearance. Patients with gastro-oesophageal reflux disease exhibit a pharmacokinetic pattern similar to that in healthy individuals, whereas elderly individuals exhibited a slightly lower metabolism rate. Patients with a severe deficit in their liver function had a lower rate of metabolism, as would be expected, whereas those with mild to moderate liver disease did not exhibit any alteration in the pharmacokinetics. The pharmacokinetics of esomeprazole in individuals with impaired renal function is unlikely to differ from that in healthy individuals. A slight sex difference in the pharmacokinetics of esomeprazole was demonstrated in that the AUC and peak plasma drug concentration were slightly, but not statistically significantly, higher in females than in males.     

Suppression of gastric acid with intravenous esomeprazole and omeprazole: results of 3 studies in healthy subjects

OBJECTIVE: To identify the optimal pharmacodynamic dosing regimen for esomeprazole administered intravenously (i.v.) and to compare acid suppression with various esomeprazole i.v. and omeprazole i.v. dosing regimens. METHODS: A total of 90 healthy Helicobacter pylori-negative subjects participated in three randomized, crossover studies of esomeprazole i.v. Comparative acid output study: an open-label study that compared single 40 mg i.v. doses (administered over 30 min) of esomeprazole and omeprazole. Dose-ranging study: an open-label study that compared acid control with five different doses of esomeprazole i.v., administered over 24 h. Comparative pH study: a double-blind study that compared esomeprazole i.v. and omeprazole at doses of 80 mg (over 30 min) + 8 mg/h (for 23.5 h). RESULTS: In the comparative acid output study, estimated mean pentagastrin-stimulated acid output was reduced from 33.9 mmol/h at baseline to 5.4 mmol/h at 4 - 5.5 h with esomeprazole vs. 9.5 mmol/h with omeprazole (p < 0.001). In the dose-ranging study, the 80 + 8 mg/h regimen provided a greater mean time with pH > 6 (12.6 h) than the lower doses (11.0 and 10.7 h for 40 + 8 mg/h and 80 + 4 mg/h, respectively) and significantly more time with pH > 4 (21.5 vs. 19.7 and 19.2 h, respectively; p < 0.05). In the comparative pH study, the mean number of h with pH > 4 was similar between esomeprazole (21.4 h) and omeprazole (21.1 h). CONCLUSIONS: Esomeprazole was superior to omeprazole in reducing stimulated acid secretion. Control of intragastric pH was similar for esomeprazole and omeprazole at a dose of 80 + 8 mg/h. An esomeprazole i.v. dosage regimen of 80 + 8 mg/h appeared to be optimal for acid suppression in healthy subjects under study.     

Effects of rabeprazole, 20 mg,or esomeprazole, 20 mg,on 24-h intragastric pH and serum gastrin in healthy subjects

AIM: To compare the antisecretory effects of rabeprazole and esomeprazole in an open, randomized, two-way crossover, clinical pharmacology study. METHODS: Twenty-four healthy subjects (14 men, 10 women; mean age 26.8 years) received rabeprazole 20 mg or esomeprazole 20 mg daily on days 1-5, with a 14-day 'wash-out'. Intragastric pH was recorded continuously, and serum gastrin measured, on days 0, 1 and 5. RESULTS: On day 0, mean intragastric pH AUC was significantly higher before the esomeprazole than before the rabeprazole treatment in four of the five time intervals analysed. On days 1 and 5, mean intragastric pH AUC was higher after rabeprazole than esomeprazole during 5-11, 14-24 and 0-24 h after dosing. Mean pH AUC in the first 5 h after dosing on day 5 was higher after esomeprazole than rabeprazole (P=0.012). On day 1, mean per cent times pH > 3 and > 4 were significantly greater after rabeprazole than esomeprazole during 0-14, 14-24 and 0-24 h. On day 5, mean serum gastrin AUC0-4 was higher (P = 0.017) after rabeprazole than esomeprazole (335 vs. 316 pg/mL.h). CONCLUSION: In this clinical pharmacology study, rabeprazole 20 mg daily was more effective than esomeprazole 20 mg daily in increasing intragastric pH and maintaining pH > 3 and > 4. On day 5, mean pH AUC was higher after esomeprazole than rabeprazole.     

Review of esomeprazole in the treatment of acid disorders

Esomeprazole (Nexium, AstraZeneca) is the (S)-isomer of omeprazole and the first proton pump inhibitor to be developed as an optical isomer. Esomeprazole has an improved pharmacokinetic profile, resulting in increased systemic exposure and less interindividual variability compared with omeprazole, and more effective suppression of gastric acid production compared with other proton pump inhibitors. In several large, double-blind, randomised trials, significantly higher rates of endoscopically-confirmed healing of erosive oesophagitis and resolution of heartburn have been achieved in patients with gastro-oesophageal reflux disease receiving 8 weeks of esomeprazole 40 mg o.d. compared with those receiving omeprazole 20 mg o.d. or lansoprazole 30 mg o.d. In the maintenance of healed erosive oesophagitis, esomeprazole 10, 20 or 40 mg o.d. was significantly more effective than placebo in two 6-month, randomised, double-blind trials. Additionally, esomeprazole 20 mg o.d. was more effective than lansoprazole 15 mg in the maintenance of healed erosive oesophagitis in another 6-month, randomised, double-blind trial. Healing of oesophagitis was also effectively maintained by esomeprazole 40 mg o.d. in a 12-month non-comparative trial. Esomeprazole 20 or 40 mg o.d. effectively relieved heartburn in patients with gastro-oesophageal reflux disease without oesophagitis in two 4-week, placebo-controlled trials. Clinical trials have shown that triple therapy with esomeprazole 40 mg o.d. in combination with amoxicillin and clarithromycin produced Helicobacter pylori eradication rates similar to those obtained using triple therapy involving twice-daily dosing with other proton pump inhibitors. Esomeprazole is well-tolerated, with a spectrum and incidence of adverse events similar to those associated with omeprazole.     

The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety

BACKGROUND: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer. In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole. AIM: This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis. METHODS: In this 6-month US multicentre randomized double-blind placebo-controlled trial, 375 Helicobacter pylori-negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end-point was maintenance of healing at 6 months. Secondary end-points assessed changes in symptoms, and long-term safety and tolerability. RESULTS: Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups. CONCLUSIONS: Esomeprazole is effective and well-tolerated in the maintenance of healing of erosive oesophagitis. Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients.     

Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors

BACKGROUND: Rapid and consistent acid suppression on the first day of dosing may be important in treating acid-related disorders. AIM: To compare the antisecretory activity and onset of action of single doses of rabeprazole, lansoprazole, pantoprazole, omeprazole capsule, omeprazole multiple unit pellet system (MUPS) tablet and placebo in healthy Helicobacter pylori-negative subjects. METHODS: This cross-over, double-blind, randomized study was performed in 18 H. pylori-negative subjects. Twenty-four-hour intragastric pH monitoring was performed on the day of treatment (once-daily dose of rabeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, omeprazole capsule 20 mg, omeprazole MUPS tablet 20 mg or placebo). RESULTS: The intragastric pH (3.4) and time at pH > 4 during the 24 h post-dose (8.0 h) were significantly greater with rabeprazole than with lansoprazole, pantoprazole, omeprazole capsule, omeprazole MUPS tablet or placebo (P 相似文献   

Effect of intravenous esomeprazole 40 mg and pantoprazole 40 mg on intragastric pH in healthy subjects. A prospective, open, randomised, two-way cross-over comparative study

OBJECTIVE: The aim of this study was to compare the effect on intragastric acidity over 24 h on days 1 and 3 following treatment with intravenous (i.v.) esomeprazole 40 mg (CAS for esomeprazole sodium: 161796-78-7) and pantoprazole 40 mg (CAS for pantoprazole sodium: 138786-67-1). METHODS: In an open, randomised, two-way cross-over study, 36 healthy volunteers received esomeprazole (Nexium) 40 mg or pantoprazole 40 mg, both administered once daily as an i.v. bolus injection for 3 consecutive days. Continuous 24-h pH recordings were made under standardised conditions at baseline and on days 1 and 3 of each treatment period. The primary variable was the percentage of time with intragastric pH > 4 during a 24-h period. RESULTS: Time with intragastric pH > 4 was significantly greater with esomeprazole than with pantoprazole during the first 4 h (47.8% vs. 18.9%), as well as for the 24-h period of day 1 and day 3 (day 1: 38.8% vs. 23.7%; day 3:55.0% vs. 35.2%, p < 0.0001 for all times examined). Mean of median intragastric pH with esomeprazole was significantly higher than with pantoprazole during the 24-h period (day 1:3.2 vs. 2.2, p < 0.0001; day 3: 4.3 vs. 3.1, p < 0.00001). CONCLUSION: Esomeprazole administered as a 40 mg i.v. bolus injection provided faster and more effective control of intragastric acidity than a 40 mg i.v. bolus injection of pantoprazole, and also maintained pH > 4 longer both during the first 4 h on day 1 and during the 24-h period of day 1 and day 3 of dosing.     

Intragastric acidity during administration of generic omeprazole or esomeprazole - a randomised, two-way crossover study including CYP2C19 genotyping

Background Generic omeprazole has been approved in many countries for the treatment of acid‐related gastrointestinal disorders. However, clinical studies comparing generic to original proton pump inhibitors are limited. Aims To compare the effect of generic omeprazole 20 mg/day with esomeprazole 20 mg/day on intragastric acidity and to investigate the influence of the CYP2C19 metabolizer status. Methods In this randomised, single‐blinded, two‐way crossover study, 24 healthy Helicobacter pylori‐negative subjects, received generic omeprazole (Omep; Hexal AG, Holzkirchen, Germany) 20 mg once daily or esomeprazole 20 mg once daily for five consecutive days. Twenty‐four‐hour intragastric pH was recorded on day 5 of each treatment. CYP2C19 status was determined by polymerase chain reaction–restriction fragment length polymorphism. Results Over all, there were no statistically significant differences between generic omeprazole and esomeprazole with respect to median intragastric pH (3.5 and 3.9, P = 0.07), the total hours with intragastric pH >4 (10.4 and 11.3, P = 0.29), and during upright (9.6 and 9.1, P = 0.77) or supine (2.2 and 2.2, P = 0.94) position. However, in CYP2C19 rapid metabolizers, esomeprazole was superior to omeprazole, with the percentage of time with intragastric pH >3.0 and pH >3.5 being higher with esomeprazole than with generic omeprazole [Δ = 9% (P = 0.026) and Δ = 8% (P = 0.046), respectively]. Conclusions Overall, generic omeprazole 20 mg appears to provide a similar intragastric acid control when compared with esomeprazole 20 mg. However, esomeprazole might be advantageous in subjects with a rapid CYP2C19 metabolizer status.     

Esomeprazole: a clinical review.

The pharmacology, pharmacodynamics, pharmacokinetics, clinical efficacy, and adverse effects of esomeprazole are reviewed. Esomeprazole, a proton-pump inhibitor (PPI), is the S-isomer of omeprazole. Esomeprazole has FDA-approved labeling for use in the treatment of symptomatic gastroesophageal reflux disease (GERD), including healing and maintenance of healing of erosive esophagitis and as part of a triple-drug regimen for Helicobocter pylori infection. Esomeprazole is structurally similar to other PPIs but is the first PPI to include only the active isomer, which may lead to improved pharmacokinetic and pharmacodynamic characteristics. Esomeprazole maintains intragastric pH at a higher level and above 4 for a longer period than other PPIs. Clinical studies have shown that esomeprazole is at least equivalent in safety and efficacy to other drugs in the class. Esomeprazole has demonstrated efficacy in the treatment of erosive esophagitis, the maintenance of healing of erosive esophagitis, and the treatment of signs and symptoms of GERD. Effective dosages are 20 or 40 mg orally every day or as needed. Esomeprazole magnesium 40 mg once daily in combination with amoxicillin and clarithromycin is effective in eradicating H. pylori infection. The potential for interacting with other drugs is limited and is similar to that of omeprazole. The most common adverse effects are headache, respiratory infection, and abdominal symptoms. Esomeprazole has pharmacokinetic properties that may make it more effective than omeprazole in some patients.     

4种质子泵抑制剂治疗胃食管反流病的临床观察

目的:比较4种质子泵抑制剂埃索美拉唑(esomeprazole)、奥美拉唑(omeprazole)、兰索拉唑(lansoprazole)和雷贝拉唑(rabeprazole)对胃食管反流病(GERD)患者,在胃酸分泌、控制症状、治愈食管炎等方面的影响。方法:将经胃镜诊断明确的124例GERD患者随机分为A,B,C,D 4组,分别给予埃索美拉唑40 mg·d~(-1),奥美拉唑40 mg·d~(-1),兰索拉唑30 mg·d~(-1),雷贝拉唑20 mg·d~(-1),qd,疗程均为4周。结果:4种质子泵抑制剂症状缓解率分别为93.1%,81.6%,85.7%和86.4%,内镜下食管炎治愈率在70%以上(P<0.05)。结论:埃索美拉唑在症状缓解率和内镜下食管炎治愈率明显优于其他3种质子泵抑制剂。