GERD is associated with substantial reductions in subjective well-being, lower work productivity, and increased healthcare use. The GERD in the Asia Pacific Survey (GAPS) found that GERD had a negative impact on well-being for 94% of respondents in terms of stress (68% of respondents), restrictions to daily activities (50%), and reduced work productivity (65%).

Nocturnal symptoms were a particular concern for this group, with 57% of respondents experiencing night-time symptoms. Nocturnal symptoms have been shown to severely impact subjective well-being and daytime functioning in several studies, and have been noted in up to 90% of patients with GERD.

The mainstay of treatment for GERD is proton pump inhibitor (PPI) therapy, which is superior to histamine-2 receptor antagonists and antacids.

There are several PPIs available, although many Asian patients with GERD continue to experience symptoms despite treatment with PPIs, suggesting an unmet need in the current treatment of GERD.

PPIs are the most effective therapy for patients with GERD. The factors involved in successful treatment include degree of acid suppression, duration of suppression over the 24-hour period, and duration of treatment.

Clinical Limitations of Conventional Proton Pump Inhibitors

While PPIs are widely regarded as the “gold-standard” of GERD treatment, there are a number of clinical limitations to currently available PPIs.

PPIs are associated with limited ability to fully relieve the discomfort of GERD, particularly at night.

The GERD in the Asia Pacific Survey (GAPS) found that only 23% of respondents felt that their pain was completely controlled with PPIs and 94% continued to experience breakthrough symptoms

In particular, 45% of respondents found that treatment for nocturnal pain was unsatisfactory.

The active ingredient in a PPI must be present in high concentrations when the proton pumps are stimulated before and during a meal.

As PPIs are acid labile, they need protection from degradation in the stomach by enteric coating or buffering.

PPIs are rapidly absorbed and subsequently eliminated, leading to a short plasma half-life and ultimately restricting their administration to before meals to achieve their full effect. As pre-meal dosing is inconvenient, this may lead to poor adherence.

The effects of PPIs tend to diminish during the 24-hour period enabling resumption of gastric acid secretion.

Adverse Interactions with Antiplatelet Therapy

Although PPIs are generally regarded as safe drugs, with any adverse effects being mostly mild and self-limiting, recent concerns have been raised about a possible interaction between some PPIs and clopidogrel.

A higher clopidogrel–PPI interaction has been observed in patients treated with omeprazole than in those treated with pantoprazole, esomeprazole, or rabeprazole.

Dexlansoprazole, lansoprazole, and pantoprazole have less effect on the antiplatelet activity of clopidogrel than do omeprazole or esomeprazole.

Why Dexlansoprazole is superior than other PPI?

Dual Delayed Release Formulation

Dexlansoprazole is a novel formulation that employs a dual delayed release technology designed to prolong the concentration–time profile and provide an extended duration of acid suppression.

The dual delayed release technology uses 2 types of enteric-coated granules with different pH-dependent dissolution profiles to provide an initial drug release in the proximal small intestine, at a pH of approximately 5.5, followed several hours later by another drug release at more distal regions of the small intestine, at a pH of ≥ 6.75.

Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication.

The FDA approved dexlansoprazole for the treatment of heartburn associated with symptomatic non-erosive GERD, healing of erosive esophagitis (EE) and maintenance of healed EE at doses of 30 mg and 60 mg once daily.

Pharmacokinetics

The plasma concentration–time profile for dexlansoprazole at steady state is characterized by two distinct peaks and prolonged drug exposure during the 24-hour dosing interval. The first peak occurred approximately 1–2 hours after dosing and the second occurred approximately 4–5 hours after dosing (time to maximum concentration was achieved at 5.0–5.4 hours), providing extended drug exposure.

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