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.


OBJECTIVE
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.
Katz
P O
PO
Division of Gastroenterology and Nutrition, Albert Einstein Medical Center, Philadelphia, PA 19141, USA. pkatz19512@aol.com
Castell
D O
DO
Chen
Y
Y
Andersson
T
T
Sostek
M B
MB
D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D064098:Esomeprazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D008297:Male
D000897:Anti-Ulcer Agents; D064098:Esomeprazole