Christopher R Emerson1, Nino Marzella. 1. Division of Pharmacy Practice, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, USA.
Abstract
BACKGROUND: Dexlansoprazole, the dextrorotatory enantiomer of lansoprazole, is a proton pump inhibitor (PPI) formulated to have dual delayed-release properties. It is indicated for healing all grades of esophagitis, maintaining the healing of erosive esophagitis (EE), and treating heartburn associated with nonerosive gastroesophageal reflux disease. OBJECTIVE: This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of dexlansoprazole, as well as its clinical efficacy and tolerability. METHODS: MEDLINE (1966-April 2010) and International Pharmaceutical Abstracts (1970-April 2010) were searched for original research and review articles published in English using the terms dexlansoprazole and TAK-390MR. The reference lists of identified articles were reviewed for additional pertinent publications. Abstracts from 2007-2009 American College of Gastroenterology and Digestive Disease Week meetings were searched using the same terms. RESULTS: By irreversibly binding to H(+)K(+)-ATPase, dexlansoprazole inhibits acid production by the parietal cell. Its dual delayed-release formulation provides 2 distinct releases of medication, prolonging the mean residence time compared with lansoprazole (5.56-6.43 vs 2.83-3.23 hours, respectively). In 2 identical Phase III trials of the healing of EE, there were no significant differences in rates of complete healing after 8 weeks between dexlansoprazole 60 and 90 mg once daily and lansoprazole 30 mg once daily. In 2 studies of the maintenance of healing of EE, rates of healing at 6 months were significantly higher with dexlansoprazole 30, 60, and 90 mg once daily compared with placebo (P < 0.001). Patients with nonerosive reflux disease who received dexlansoprazole 30 or 60 mg once daily had significantly more 24-hour heartburn-free days compared with those who received placebo (P < 0.001). Dexlansoprazole was well tolerated compared with placebo or lansoprazole in all studies. CONCLUSIONS: In the studies reviewed, dexlansoprazole was well tolerated and effective in the healing and maintenance of EE, and in the treatment of nonerosive reflux disease. However, most of the available evidence involved comparisons with placebo, making it difficult to draw meaningful conclusions about the place of dexlansoprazole among PPIs. More head-to-head comparative trials with other PPIs are needed to determine whether the unique formulation of dexlansoprazole translates into a clinically meaningful improvement in outcomes.
BACKGROUND:Dexlansoprazole, the dextrorotatory enantiomer of lansoprazole, is a proton pump inhibitor (PPI) formulated to have dual delayed-release properties. It is indicated for healing all grades of esophagitis, maintaining the healing of erosive esophagitis (EE), and treating heartburn associated with nonerosive gastroesophageal reflux disease. OBJECTIVE: This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of dexlansoprazole, as well as its clinical efficacy and tolerability. METHODS: MEDLINE (1966-April 2010) and International Pharmaceutical Abstracts (1970-April 2010) were searched for original research and review articles published in English using the terms dexlansoprazole and TAK-390MR. The reference lists of identified articles were reviewed for additional pertinent publications. Abstracts from 2007-2009 American College of Gastroenterology and Digestive Disease Week meetings were searched using the same terms. RESULTS: By irreversibly binding to H(+)K(+)-ATPase, dexlansoprazole inhibits acid production by the parietal cell. Its dual delayed-release formulation provides 2 distinct releases of medication, prolonging the mean residence time compared with lansoprazole (5.56-6.43 vs 2.83-3.23 hours, respectively). In 2 identical Phase III trials of the healing of EE, there were no significant differences in rates of complete healing after 8 weeks between dexlansoprazole 60 and 90 mg once daily and lansoprazole 30 mg once daily. In 2 studies of the maintenance of healing of EE, rates of healing at 6 months were significantly higher with dexlansoprazole 30, 60, and 90 mg once daily compared with placebo (P < 0.001). Patients with nonerosive reflux disease who received dexlansoprazole 30 or 60 mg once daily had significantly more 24-hour heartburn-free days compared with those who received placebo (P < 0.001). Dexlansoprazole was well tolerated compared with placebo or lansoprazole in all studies. CONCLUSIONS: In the studies reviewed, dexlansoprazole was well tolerated and effective in the healing and maintenance of EE, and in the treatment of nonerosive reflux disease. However, most of the available evidence involved comparisons with placebo, making it difficult to draw meaningful conclusions about the place of dexlansoprazole among PPIs. More head-to-head comparative trials with other PPIs are needed to determine whether the unique formulation of dexlansoprazole translates into a clinically meaningful improvement in outcomes.