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.
RCT Entities:
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.