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Delayed release dexlansoprazole in the treatment of GERD and erosive esophagitis.

Wittbrodt ET, Baum C, Peura DA - Clin Exp Gastroenterol (2009)

Bottom Line: Dexlansoprazole MR is the (R)-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional single-release PPI.Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg.The safety profile of dexlansoprazole MR is similar to that of lansoprazole.

View Article: PubMed Central - PubMed

Affiliation: Takeda Pharmaceuticals North America, Inc.

ABSTRACT
Although proton pump inhibitors (PPI) have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD), several treatment challenges with PPI have emerged. Dexlansoprazole MR is the (R)-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional single-release PPI. Dexlansoprazole MR can be administered without regard to meals or the timing of meals in most patients. Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg. Superior relief of heartburn occurred in patients taking dexlansoprazole MR 30 mg (55% heartburn-free 24-hour periods) vs placebo (14%) for symptomatic nonerosive GERD. The safety profile of dexlansoprazole MR is similar to that of lansoprazole. The extended pharmacodynamic effects, added convenience, and efficacy and safety of dexlansoprazole MR offer a novel approach to gastric pH control in patients with acid-related disorders.

No MeSH data available.


Related in: MedlinePlus

Mean time-concentration profiles of dexlansoprazole MR on Day 5. Adapted by permission from Informa Healthcare Vakily M, Zhang W, Wu J, Atkinson SN, Mulford D. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel dual delayed release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med Res Opin. 2009;25(3):627–638.19 Copyright © 2009.
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f1-ceg-2-117: Mean time-concentration profiles of dexlansoprazole MR on Day 5. Adapted by permission from Informa Healthcare Vakily M, Zhang W, Wu J, Atkinson SN, Mulford D. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel dual delayed release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med Res Opin. 2009;25(3):627–638.19 Copyright © 2009.

Mentions: The elimination half-life of dexlansoprazole is approximately 1–2 hours in healthy subjects and in patients with symptomatic GERD; this is similar to other PPI. The Dual Delayed Release formulation (DDR™) employed in delivering dexlansoprazole is a more significant factor in prolonging drug residence time in the body after oral administration than the inherently slower clearance of dexlansoprazole as compared to the (S)-enantiomer. The DDR formulation delivers 2 drug inputs in the proximal and more distal small intestine. Distinct pH-dependent releases of drug are designed to occur from two types of enteric-coated granules housed in a gelatin capsule. Upon dissolution of the outer capsule in the stomach, the first type of granule is designed to release quickly after the granules reach the proximal duodenum providing an initial drug release profile similar to that of lansoprazole and resulting in an initial peak in plasma dexlansoprazole concentrations within 1 to 2 hours of capsule ingestion. The second release from the remaining granules is designed to release farther along the gastrointestinal tract at the distal portion of the small intestine and creates a second drug peak in plasma dexlansoprazole concentrations within 4 to 5 hours of capsule ingestion. The purpose of the second release is to provide a greater amount of drug to be absorbed later in the dosing interval in order to provide extended duration of acid suppression. Therefore, the resulting time-concentration profile of dexlansoprazole MR reveals a two-peaked pattern that extends to approximately 12 hours after a dose is ingested (Figure 1).


Delayed release dexlansoprazole in the treatment of GERD and erosive esophagitis.

Wittbrodt ET, Baum C, Peura DA - Clin Exp Gastroenterol (2009)

Mean time-concentration profiles of dexlansoprazole MR on Day 5. Adapted by permission from Informa Healthcare Vakily M, Zhang W, Wu J, Atkinson SN, Mulford D. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel dual delayed release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med Res Opin. 2009;25(3):627–638.19 Copyright © 2009.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108635&req=5

f1-ceg-2-117: Mean time-concentration profiles of dexlansoprazole MR on Day 5. Adapted by permission from Informa Healthcare Vakily M, Zhang W, Wu J, Atkinson SN, Mulford D. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel dual delayed release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med Res Opin. 2009;25(3):627–638.19 Copyright © 2009.
Mentions: The elimination half-life of dexlansoprazole is approximately 1–2 hours in healthy subjects and in patients with symptomatic GERD; this is similar to other PPI. The Dual Delayed Release formulation (DDR™) employed in delivering dexlansoprazole is a more significant factor in prolonging drug residence time in the body after oral administration than the inherently slower clearance of dexlansoprazole as compared to the (S)-enantiomer. The DDR formulation delivers 2 drug inputs in the proximal and more distal small intestine. Distinct pH-dependent releases of drug are designed to occur from two types of enteric-coated granules housed in a gelatin capsule. Upon dissolution of the outer capsule in the stomach, the first type of granule is designed to release quickly after the granules reach the proximal duodenum providing an initial drug release profile similar to that of lansoprazole and resulting in an initial peak in plasma dexlansoprazole concentrations within 1 to 2 hours of capsule ingestion. The second release from the remaining granules is designed to release farther along the gastrointestinal tract at the distal portion of the small intestine and creates a second drug peak in plasma dexlansoprazole concentrations within 4 to 5 hours of capsule ingestion. The purpose of the second release is to provide a greater amount of drug to be absorbed later in the dosing interval in order to provide extended duration of acid suppression. Therefore, the resulting time-concentration profile of dexlansoprazole MR reveals a two-peaked pattern that extends to approximately 12 hours after a dose is ingested (Figure 1).

Bottom Line: Dexlansoprazole MR is the (R)-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional single-release PPI.Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg.The safety profile of dexlansoprazole MR is similar to that of lansoprazole.

View Article: PubMed Central - PubMed

Affiliation: Takeda Pharmaceuticals North America, Inc.

ABSTRACT
Although proton pump inhibitors (PPI) have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD), several treatment challenges with PPI have emerged. Dexlansoprazole MR is the (R)-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional single-release PPI. Dexlansoprazole MR can be administered without regard to meals or the timing of meals in most patients. Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg. Superior relief of heartburn occurred in patients taking dexlansoprazole MR 30 mg (55% heartburn-free 24-hour periods) vs placebo (14%) for symptomatic nonerosive GERD. The safety profile of dexlansoprazole MR is similar to that of lansoprazole. The extended pharmacodynamic effects, added convenience, and efficacy and safety of dexlansoprazole MR offer a novel approach to gastric pH control in patients with acid-related disorders.

No MeSH data available.


Related in: MedlinePlus