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.
BACKGROUND
Dexlansoprazole MR is a Dual Delayed Release proton pump inhibitor formulated to extend the duration of acid suppression.


OBJECTIVE
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.


CONCLUSIONS
Dexlansoprazole MR provides comparable acid control when administered at different times of the day.
Lee
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RD
Research & Development, Takeda Global Research & Development Center, Inc., Deerfield, IL 60015, USA. ronald.lee@tgrd.com
Mulford
D
D
Wu
J
J
Atkinson
S N
SN
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics / Q000627:therapeutic use; D064748:Dexlansoprazole; D005260:Female; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D003692:Delayed-Action Preparations; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064748:Dexlansoprazole