Dexilant (dexlansoprazole) is a new-generation proton pump inhibitor (PPI) that is licensed to treat gastroesophageal reflux disease (GERD) in children and adults. While PPIs are the mainstay of treatment in acid-related conditions, dexlansoprazole has a unique dual-release formulation that sets it apart from its contemporaries. It produces a peak plasma level at about one hour after administration. Its second component then produces a second peak after four hours, further extending its therapeutic effects.
In the early 1990s, a new class of drugs called proton pump inhibitors entered the US market and revolutionized the treatment of acid peptic disorders. Up to this day, they are considered the best therapeutic option for GERD. Not surprisingly, they are also the first-line treatment for non-erosive reflex disease (NERD), functional dyspepsia, Zollinger-Ellison syndrome, peptic ulcer disease, and prevention of nonsteroidal anti-inflammatory drugs (NSAID) associated ulcers.
What makes Dexilant different?
GERD occurs when there is backward flow of acid from the stomach, causing heartburn and possible damage to the esophagus. Dexilant treats the symptoms of GERD, allowing the injured esophagus to heal, and prevent further damage. Just like any PPI, it works by reducing the amount of acid produced in the stomach. Dexlansoprazole is the fifth FDA-approved PPI with a somewhat different characteristic and pharmacological properties than lansoprazole (trade name: Prevacid). Lansoprazole is a chiral drug and dexlansoprazole is its second enantiomer (right mirror image), the other one being esomeprazole. Takeda pharmaceuticals designed Dexilant (former Kapidex) with a special dual-release mechanism that produces two peak plasma concentrations. This modification resulted to the drug’s improved bioavailability, metabolism, and more efficient proton pump inhibition.
Following administration, the active ingredient of Dexilant is released in two phases at specific pH values and time intervals. Imagine two types of granules in one capsule of Dexilant—the first type, representing a quarter of the drug’s dose, is released at the proximal duodenum, which has a pH of 5.5. The remaining granules are released in the distal small intestine at a 6.75 pH level. The drug achieves its first peak plasma concentration within one to two hours and another within four to five hours after administration. This is to ensure a long period of drug exposure to provide a more powerful inhibitory effect over other available PPIs.
Twice-daily dosing is not required
Most PPIs have short plasma have lives, which translates to shorter duration of effect. In a number of patients, a second dose is necessary to relieve symptoms at night. Still, 40% of these patients up their dose because of persistent nighttime symptoms also referred to as “nocturnal acid breakthrough.” This is a common issue among patients taking a single-release, once-daily morning dose of PPI. Dexilant stays longer in the serum, thus twice daily dosing is not required. Thanks to its dual release mechanism, which is comparable to taking a second dose.
Not affected by food
PPIs are usually taken 30 minutes before the first meal of the day for maximal effect. PPI agents bind to 70–80% of active pumps irreversibly, but newer proton pumps are being produced for continued gastric acid secretion. In most cases, a single dose of PPI is not enough to prevent all acid secretions. By taking a second dose, more pumps become irreversibly bound to the drug and gastric acid inhibition is increased. Dexilant lacks an adverse interaction with food, so it’s unnecessary to take the drug prior to a meal. However, taking the drug after a high-fat meal has shown an increase in maximum plasma concentration by 12–31%, but it produces no clinically significant differences in gastric pH. Other PPIs that can be taken without regard to food include pantoprazole and rabeprazole.
In two head-to-head trials comparing dexlansoprazole to lansoprazole for the treatment of erosive esophagitis, dexlansoprazole at 60 and 90mg were found to be non-inferior to 30mg of lansoprazole, but superiority results were inconsistent. However, in placebo-controlled trials, dexlansoprazole has demonstrated high efficacy for symptomatic relief of NERD and maintenance therapy of healed erosive esophagitis. In a 24-hour period following administration, this novel drug increases the percentage of time that intragastric pH remains at >4, the standard measurement of acid suppression for treating acid-related diseases. When the drug is taken for 5 days, dexlansoprazole kept the gastric pH at >4 for 17 hours per day, compared to the 14 hours per day of lansoprazole.