Managing Gastroesophageal Reflux Disease (GERD)-comparative efficacy and outcomes of Dexlansoprazole MR
The management of gastroesophageal reflux disease (GERD) has been revolutionized with the development of proton pump inhibitors (PPIs). Unfortunately, due to the inherent pharmacokinetic and pharmacodynamic profiles of conventional PPIs, many patients continue to suffer from symptoms related to GERD despite appropriate use of PPIs.
Current approaches for the management of GERD focus on lifestyle interventions as well as pharmacologic therapy. Traditional recommendations for lifestyle modifications have included weight loss, head-of-bed elevation, and avoidance of meals 2–3 hours prior to sleep. Elimination of tobacco and alcohol, as well as dietary changes including avoidance of chocolate, caffeine, spicy foods, citrus, and carbonated beverages, has also been advocated.
American College of Gastroenterology and American Gastroenterological Association guidelines advocate the use of proton pump inhibitors (PPIs) in both treatment and maintenance of healing of erosive esophagitis. Patients with nonerosive disease are advised to use either H2 receptor antagonists or PPIs for symptom relief.
TAKE HOME MESSAGE:
Dexlansoprazole MR is a PPI with a unique dual delayed-release delivery system that has been designed to address the unmet needs in GERD management.
The drawbacks of conventional PPI therapy primarily involve limitations in the underlying pharmacokinetic and pharmacodynamic properties of the drugs. This is manifested in the need for mealtime dosing and the short half-lives of these drugs.
Dexlansoprazole MR has been designed to effectively address these issues by prolonging PPI pharmacokinetic and pharmacodynamic profiles.
In addition, dexlansoprazole MR has been shown to be effective in several specific clinical situations. These include coadministration with clopidogrel, healing of all grades of erosive esophagitis, improvement in reflux-related quality of life, step down to once-per-day dosing, and treatment of Helicobacter pylori infections.
Furthermore, dexlansoprazole MR has been found to induce symptom improvement in patients with nonerosive esophageal reflux disease, nocturnal heartburn and GERD-related sleep disturbance, and regurgitation. Overall, dexlansoprazole MR is a unique and useful tool in the management of GERD.
Comparison of Dexlansoprazole MR and other PPIs
While there are no direct comparisons of dexlansoprazole MR with PPIs other than lansoprazole, an indirect comparison of randomized controlled trials of dexlansoprazole in the treatment of erosive esophagitis healing, maintenance of healed erosive esophagitis, and treatment of NERD suggested better treatment effect of dexlansoprazole MR in symptom control in NERD. However, there was no significant difference in erosive esophagitis outcomes.
Dexlansoprazole MR’s place in therapy
Dexlansoprazole MR can be considered for patients with varying manifestations of GERD, including those with a new diagnosis of GERD, erosive esophagitis, or need for maintenance of healing of erosive esophagitis, as well as symptomatic nonerosive GERD.
Additionally, patients who require 24-hour symptom relief, experience nocturnal symptoms, have incomplete response to once-daily conventional PPI therapy, are obese, use clopidogrel, or require dosing flexibility are all excellent candidates for treatment with dexlansoprazole MR.
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Conventional PPIs have a short half-life, often resulting in breakthrough symptoms and necessitating more frequent dosing
Dexlansoprazole is the R-enantiomer of lansoprazole. It is highly protein bound and undergoes elimination via hepatic biotransformation.
It is the delivery system, rather than the inherently slower hepatic clearance, that prolongs the plasma residence time of dexlansoprazole MR. The dual delayed-release technology incorporates two distinct sets of enteric-coated granules that are designed to offer two distinct, pH-dependent releases of drug.
After ingestion, the gelatin capsule containing the granules dissolves in the stomach, and the first set of granules (~25% of the drug dose) is released into the proximal duodenum (pH 5.5). This results in an early rise in plasma concentration (1–2 hours), similar to other PPIs. The remaining granules (75%) are designed to be released in the distal small intestine (pH 6.75), resulting in a second concentration peak at 4–5 hours after ingestion. This delivery system provides a prolonged duration of acid suppression and helps to limit the necessity for more than once-daily dosing.
Results showed the average 24-hour intragastric pH following a single dose of dexlansoprazole MR was higher compared to a single dose of esomeprazole (58% versus 48%;) The most profound difference was noted in the second half of the day, presumably due to the longer duration of action of dexlansoprazole MR.
For maximum efficacy, typical PPIs must be dosed prior to meals
Parietal cell proton pumps are activated with meals, and the majority of pumps are inserted with the morning meal. Typical PPIs inhibit stimulated acid secretion, and are recommended to be taken prior to food consumption, particularly 30–60 minutes prior to the morning meal, in order to maximize acid suppression. This requirement can be burdensome for many patients and can lead to issues with continued symptoms. On the other hand, due to its prolonged duration of action, dexlansoprazole MR inhibits both basal and stimulated gastric acid secretion, and is effective regardless of food consumption.
The investigators concluded that food as well as timing of intake of dexlansoprazole MR dosing relative to a meal did not impact the drugs ability to inhibit acid.
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