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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 dexlansoprazole plasma concentration-time profiles A), Cmax B), and AUC C) following a single dose of dexlansoprazole MR 90 mg under fasted and various fed conditions. Reproduced with permission from Lee RD, Vakily M, Mulford D, Wu J, Atkinson SN. Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel dual delayed release formulation of a proton pump inhibitor – evidence for dosing flexibility. Aliment Pharmacol Ther. 2009; 29(8):824–833.23 Copyright © 2009 Wiley-Blackwell.
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f3-ceg-2-117: Mean dexlansoprazole plasma concentration-time profiles A), Cmax B), and AUC C) following a single dose of dexlansoprazole MR 90 mg under fasted and various fed conditions. Reproduced with permission from Lee RD, Vakily M, Mulford D, Wu J, Atkinson SN. Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel dual delayed release formulation of a proton pump inhibitor – evidence for dosing flexibility. Aliment Pharmacol Ther. 2009; 29(8):824–833.23 Copyright © 2009 Wiley-Blackwell.

Mentions: The impact of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR was evaluated in 46 healthy subjects who completed all dosing regimens in a randomized, 4-period, open-label, crossover study.23 Placebo was administered in 4 regimens: after a 10-hour fast, 30 minutes before, 5 minutes before, or 30 minutes after a high-fat breakfast on Day 1; dexlansoprazole MR 90 mg was administered in the same fashion for each crossover period on Day 3. Plasma concentrations of dexlansoprazole were measured on Day 3 and 24-hour intragastric pH was assessed on Days 1 and 3. Pharmacokinetics of dexlansoprazole in the fed conditions (administered 5 minutes before and 30 minutes after a high-fat breakfast) when compared to the fasted state displayed at least a 1.09-fold greater increase (using the point estimates) in Cmax and AUC for the fed state (Figure 3). Thus, the bioavailability was increased in the fed vs fasted state. The data also showed that the systemic exposure of dexlansoprazole after dexlansoprazole MR was administered 30 minutes before a high-fat breakfast was bioequivalent to that obtained following administration of dexlansoprazole MR under fasted state. The differences in the pharmacodynamic parameters measured as mean 24-hour intragastric pH and % time 24-hour intragastric pH > 4 were not considered to be clinically meaningful between any of the periods which signified both a lack of food effect and a lack of effect of timing of food intake relative to dosing with dexlansoprazole MR on intragastric pH profile.


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

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

Mean dexlansoprazole plasma concentration-time profiles A), Cmax B), and AUC C) following a single dose of dexlansoprazole MR 90 mg under fasted and various fed conditions. Reproduced with permission from Lee RD, Vakily M, Mulford D, Wu J, Atkinson SN. Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel dual delayed release formulation of a proton pump inhibitor – evidence for dosing flexibility. Aliment Pharmacol Ther. 2009; 29(8):824–833.23 Copyright © 2009 Wiley-Blackwell.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ceg-2-117: Mean dexlansoprazole plasma concentration-time profiles A), Cmax B), and AUC C) following a single dose of dexlansoprazole MR 90 mg under fasted and various fed conditions. Reproduced with permission from Lee RD, Vakily M, Mulford D, Wu J, Atkinson SN. Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel dual delayed release formulation of a proton pump inhibitor – evidence for dosing flexibility. Aliment Pharmacol Ther. 2009; 29(8):824–833.23 Copyright © 2009 Wiley-Blackwell.
Mentions: The impact of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR was evaluated in 46 healthy subjects who completed all dosing regimens in a randomized, 4-period, open-label, crossover study.23 Placebo was administered in 4 regimens: after a 10-hour fast, 30 minutes before, 5 minutes before, or 30 minutes after a high-fat breakfast on Day 1; dexlansoprazole MR 90 mg was administered in the same fashion for each crossover period on Day 3. Plasma concentrations of dexlansoprazole were measured on Day 3 and 24-hour intragastric pH was assessed on Days 1 and 3. Pharmacokinetics of dexlansoprazole in the fed conditions (administered 5 minutes before and 30 minutes after a high-fat breakfast) when compared to the fasted state displayed at least a 1.09-fold greater increase (using the point estimates) in Cmax and AUC for the fed state (Figure 3). Thus, the bioavailability was increased in the fed vs fasted state. The data also showed that the systemic exposure of dexlansoprazole after dexlansoprazole MR was administered 30 minutes before a high-fat breakfast was bioequivalent to that obtained following administration of dexlansoprazole MR under fasted state. The differences in the pharmacodynamic parameters measured as mean 24-hour intragastric pH and % time 24-hour intragastric pH > 4 were not considered to be clinically meaningful between any of the periods which signified both a lack of food effect and a lack of effect of timing of food intake relative to dosing with dexlansoprazole MR on intragastric pH profile.

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