BACKGROUND: Proton pump inhibitors (PPIs) provide the most effective pharmacotherapy for treating acid-related disorders. However, PPIs do not completely control acid over 24 h with once-daily dosing. AIMS: To discuss limitations inherent in the pharmacokinetics (PK) and pharmacodynamics of conventional PPI formulations, which provide a single drug release. Also, to consider approaches to extending the duration of acid suppression focusing on dexlansoprazole MR, a PPI with a novel Dual Delayed Release (DDR) formulation. METHOD: We reviewed the available literature regarding marketed and investigational PPIs. RESULTS: Non-standard dosing of currently marketed PPIs has produced incremental advances in acid control. Multiple approaches are being evaluated to enhance acid suppression with PPIs. Dexlansoprazole MR is a DDR formulation of dexlansoprazole, an enantiomer of lansoprazole, with two distinct drug release periods to prolong the plasma dexlansoprazole concentration-time profile and extend duration of acid suppression. Clinical studies show that dexlansoprazole MR produces a dual-peak PK profile that maintains therapeutic plasma drug concentrations longer than lansoprazole, with a single-peak PK profile, and increases the percentage of time that intragastric pH >4. CONCLUSIONS: Novel drug delivery platforms, including the dexlansoprazole MR DDR formulation, may improve acid suppression and offer benefits over conventional single release PPI formulations.
BACKGROUND: Proton pump inhibitors (PPIs) provide the most effective pharmacotherapy for treating acid-related disorders. However, PPIs do not completely control acid over 24 h with once-daily dosing. AIMS: To discuss limitations inherent in the pharmacokinetics (PK) and pharmacodynamics of conventional PPI formulations, which provide a single drug release. Also, to consider approaches to extending the duration of acid suppression focusing on dexlansoprazole MR, a PPI with a novel Dual Delayed Release (DDR) formulation. METHOD: We reviewed the available literature regarding marketed and investigational PPIs. RESULTS: Non-standard dosing of currently marketed PPIs has produced incremental advances in acid control. Multiple approaches are being evaluated to enhance acid suppression with PPIs. Dexlansoprazole MR is a DDR formulation of dexlansoprazole, an enantiomer of lansoprazole, with two distinct drug release periods to prolong the plasma dexlansoprazole concentration-time profile and extend duration of acid suppression. Clinical studies show that dexlansoprazole MR produces a dual-peak PK profile that maintains therapeutic plasma drug concentrations longer than lansoprazole, with a single-peak PK profile, and increases the percentage of time that intragastric pH >4. CONCLUSIONS: Novel drug delivery platforms, including the dexlansoprazole MR DDR formulation, may improve acid suppression and offer benefits over conventional single release PPI formulations.
Authors: Amanda B Muir; Mei-Lun Wang; David Metz; Gary Falk; Jonathan Markowitz; Jonathan M Spergel; Chris A Liacouras Journal: Gut Date: 2016-07-26 Impact factor: 23.059