Dexlansoprazole

Generic Name
Dexlansoprazole
Brand Names
Dexilant
Drug Type
Small Molecule
Chemical Formula
C16H14F3N3O2S
CAS Number
138530-94-6
Unique Ingredient Identifier
UYE4T5I70X
Background

Dexlansoprazole is a new generation proton pump inhibitor (PPI) used for the management of symptoms associated with gastroesophageal reflux disease (GERD) and erosive esophagitis. Dexlansoprazole is the R-enantiomer of Lansoprazole, which is composed of a racemic mixture of the R- and S-enantiomers. Compared to the older generation of PPIs (which includes Pantoprazole, Omeprazole, and Lansoprazole) , dexlansoprazole MR has a unique pharmacokinetic profile due to its delayed-release and dual-delivery release system. The active ingredient is released in two phases at different pH values and at different time points, resulting in two peak concentrations in the blood; 25% of the dose is released at pH 5.5 in the proximal duodenum, while the remaining 75% is released at pH 6.75 in the distal small intestine . As a result, dexlansoprazole has a peak concentration within 1-2 hours after dosing and another within 4-5 hours . Dexlansoprazole's unique pharmacokinetics addresses limitations of the older generation PPIs including short plasma half-life, break-through symptoms, and need for meal-associated dosing . These characteristics make dexlansoprazole a good option for people who struggle with adherence and strict dosage timing before meals.

Dexlansoprazole exerts its stomach acid-suppressing effects in the same way as other drugs in the PPI family by inhibiting the final step in gastric acid production. Dexlansoprazole targets the (H+, K+)-ATPase enzyme, which is involved in the secretion of hydrochloric acid through the exchange of H+ ions from the cytoplasm for K+ ions. Normally functioning (H+, K+)-ATPase stimulates hydrochloric acid secretion into the gastric lumen thereby increasing stomach acidity and lowering pH. Once absorbed into circulation, dexlansoprazole covalently binds to the sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells, which leads to inhibition of both basal and stimulated gastric acid secretion. Despite dexlansoprazole's unique pharmacokinetic profile, efficacy in management of GERD symptoms is considered similar to other medications within the PPI class including Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, and Rabeprazole.

Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as dexlansoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal C. difficile), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life . PPIs such as dexlansoprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes .

Dexlansoprazole doses should be slowly lowered, or tapered, before discontinuing as rapid discontinuation of PPIs such as dexlansoprazole may cause a rebound effect and a short term increase in hypersecretion .

Indication

Dexlansoprazole is a proton pump inhibitor (PPI) indicated in patients 12 years of age and older for:

Associated Conditions
Erosive Esophagitis, Heartburn, Symptomatic Non-erosive Gastroesophageal Reflux Disease, Healed erosive esophagitis
Associated Therapies
-

Effect of Dexlansoprazole on Bone Homeostasis

First Posted Date
2010-10-07
Last Posted Date
2024-03-18
Lead Sponsor
Takeda
Target Recruit Count
115
Registration Number
NCT01216293

Can E-cadherin Found in Tissue/Blood be Valuable in Identifying & Monitoring Patients With Post-proton Pump Inhibitor (PPI)-Responsive Heartburn

First Posted Date
2010-06-23
Last Posted Date
2016-12-19
Lead Sponsor
University of North Carolina, Chapel Hill
Target Recruit Count
40
Registration Number
NCT01149395
Locations
🇺🇸

University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Does Intensive Acid Suppression Reduce Esophageal Inflammation and Recurrent Barrett's Esophagus Following Ablation?

First Posted Date
2010-03-26
Last Posted Date
2016-03-17
Lead Sponsor
Mayo Clinic
Target Recruit Count
30
Registration Number
NCT01093755
Locations
🇺🇸

Mayo Clinic in Rochester, Rochester, Minnesota, United States

Study to Evaluate the Pharmacokinetics and Safety of Dexlansoprazole in Pediatric Subjects With Symptomatic Gastroesophageal Reflux Disease

Phase 1
Completed
Conditions
Interventions
First Posted Date
2010-01-08
Last Posted Date
2012-04-05
Lead Sponsor
Takeda
Target Recruit Count
36
Registration Number
NCT01045096

Reflux Disease in Head and Neck Cancer Patients Undergoing Radiation Therapy

First Posted Date
2009-06-25
Last Posted Date
2012-09-07
Lead Sponsor
M.D. Anderson Cancer Center
Registration Number
NCT00928161

A Study of Dexlansoprazole Modified Release Formulation to Treat Night Heartburn

Phase 3
Completed
Conditions
Interventions
First Posted Date
2008-02-29
Last Posted Date
2011-04-28
Lead Sponsor
Takeda
Target Recruit Count
305
Registration Number
NCT00627016
© Copyright 2024. All Rights Reserved by MedPath