Bioavailability of a dexlansoprazole delayed-release orally disintegrating tablet: effects of food and mode of administration

Abstract

Background

Dexlansoprazole is a proton pump inhibitor (PPI) approved for use in dual delayed-release capsule and orally disintegrating tablet (ODT) formulations.

Aim

To assess effects of food, water, and route of administration on the bioavailability of dexlansoprazole 30-mg ODT.

Methods

Two separate open-label, phase 1, single-dose crossover studies were conducted in healthy adults. In study 1, pharmacokinetic parameters were analyzed in participants receiving dexlansoprazole ODT in a fed or fasted state with and without water. In study 2, the bioavailability of dexlansoprazole after administration via oral syringe or nasogastric (NG) tube, or after swallowing intact with water was compared to ODT administration in the fasted state, swallowed without water. Blood samples for determining dexlansoprazole plasma concentrations and pharmacokinetic parameter estimates were collected before and after dosing.

Results

Equivalent values for area under the plasma concentration–time curve (AUC) were observed in the fed and fasted states, but the maximum observed plasma concentration (C_max) was 38% lower in the fed state; therefore, bioequivalence was not achieved. A water rinse following standard ODT administration decreased dexlansoprazole bioavailability, with lower C_max and AUC values than when ODT was administered without a water rinse. Bioequivalence was demonstrated when comparing the alternative routes of administration, including via oral syringe or NG tube with standard ODT administration. Unlike with a water rinse, bioequivalence to standard ODT administration (i.e., without water) was demonstrated when swallowing the ODT intact with water. Rates of adverse events were comparable irrespective of administration route in the fasted state (6.7%–9.3%) and were 12% higher in the fed state than in the fasted state.

Conclusion

The AUC from the dexlansoprazole ODT was equivalent when administered in the fed and fasted states. Equivalent systemic exposure to dexlansoprazole was achieved regardless of the administration route.

Keywords:

• dexlansoprazole
• bioavailability
• proton pump inhibitor
• orally disintegrating tablet
• food effects
• mode of administration

Supplementary materials

Table S1 Study 1 treatment sequences

Table S2 Study 2 treatment sequences

Acknowledgments

Medical writing assistance was provided by Nafis Islam, PharmD, and Bomina Yu, PhD, CMPP, of inVentiv Medical Communications, which was supported by Takeda Pharmaceuticals USA, Inc. The authors thank both Dr. Michael Cwik, an employee of Takeda and the staff of PPD, Middleton, WI, for conducting the bioanalytical portion of the study. The authors also thank Ms. Angela Gamble and Ms. Kelly Hanna for managing the conduct of studies 1 and 2, respectively.

All authors had access to the data and vouch for the veracity and completeness of the data and the data analysis. Funding for this study was provided by Takeda Development Center Americas, Inc.

Author contributions

All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

All authors are employees of Takeda Development Center Americas, Inc., a wholly owned subsidiary of Takeda Pharmaceuticals America, Inc. The authors report no other conflicts of interest in this work.