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

Summary 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.