The effect of time‐of‐day dosing on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR: evidence for dosing flexibility with a Dual Delayed Release proton pump inhibitor

• Published in: Alimentary pharmacology & therapeutics Vol. 31; no. 9; pp. 1001 - 1011
• Main Authors: LEE, R. D., MULFORD, D., WU, J., ATKINSON, S. N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2010; Blackwell
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - blood; 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacokinetics; 2-Pyridinylmethylsulfinylbenzimidazoles - therapeutic use; Adolescent; Adult; Anti-Ulcer Agents - blood; Anti-Ulcer Agents - pharmacokinetics; Anti-Ulcer Agents - therapeutic use; Biological and medical sciences; Cross-Over Studies; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - therapeutic use; Dexlansoprazole; Digestive system; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Lansoprazole; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Proton Pump Inhibitors - blood; Proton Pump Inhibitors - pharmacokinetics; Proton Pump Inhibitors - therapeutic use; Time Factors; Treatment Outcome; Young Adult; Dexlansoprazole; Pharmacokinetic pharmacodynamic relationship; Benzimidazole derivatives; Controlled release form; Dosage form; Antiulcer agent; Flexibility; Posology; Proton pump inhibitor
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/j.1365-2036.2010.04272.x

Aliment Pharmacol Ther 31, 1001–1011 Summary Background  Dexlansoprazole MR is a Dual Delayed Release proton pump inhibitor formulated to extend the duration of acid suppression. Aim  To evaluate the pharmacokinetics and pharmacodynamics of dexlansoprazole MR dosed before 4 different meal times. Methods  In this randomized, open‐label, four‐way crossover study, 48 healthy subjects received dexlansoprazole MR 60 mg once daily 30 min before breakfast, lunch, dinner or an evening snack. Pharmacokinetics of dexlansoprazole MR and intragastric pH were assessed over a 24‐h postdose interval on day 5 for each regimen. Results  Absorption was delayed when dexlansoprazole MR was administered before each regimen relative to breakfast; however, systemic exposures of dexlansoprazole at all regimens were bioequivalent. There were no statistically significant differences in mean 24‐h intragastric pH between dosing before dinner or an evening snack vs. breakfast; however, there was a small (0.2), but statistically significant difference between lunch and breakfast. There was a statistically significant difference of 7 percentage points in the percentage of time intragastric pH was >4 for the snack regimen relative to the breakfast regimen, but there were no statistically significant differences between lunch or dinner compared with breakfast. Conclusion  Dexlansoprazole MR provides comparable acid control when administered at different times of the day.