Advantages of dexlansoprazole

Gastroesophageal reflux disease (GORD) is a prevalent condition affecting 8 to 33% of the global population, marked by the recurrent backflow of stomach contents into the oesophagus, leading to various oesophageal and extra-oesophageal symptoms. Proton pump inhibitors (PPIs) are commonly used for empirical treatment due to their high sensitivity (71%) and moderate specificity (44%) in diagnosing GORD compared to other methods such as pH monitoring and endoscopy.

However, PPIs have limitations. They only inhibit around 70% of acid secretion per oral administration, necessitating 2 to 3 days for complete acid suppression and offering inadequate nighttime coverage due to short half-lives and single-dose administration in the morning. To address nocturnal symptoms, strategies include doubling the dose or prescribing prolonged-release formulations like dexlansoprazole, an isomer of lansoprazole, which provides sustained acid suppression with a single daily dose.

UNIQUE ASPECTS OF DEXLANSOPRAZOLE

Dexlansoprazole offers distinct advantages over traditional PPIs in managing GORD, including prolonged acid suppression, flexible administration, and superior symptom relief. Dexlansoprazole's prolonged antisecretory activity stems from its dual delayed-release formulation, utilising granules with pH-dependent dissolution profiles for sequential drug release in the proximal and distal duodenum. This results in higher bioavailability, longer circulation time, and sustained efficacy, independent of meal times, enhancing patient compliance.

Dexlansoprazole's unique formulation releases its active component in two pulses based on pH levels: an initial release (25%) at pH 5.5 in the proximal duodenum within 1 to 2 hours and a subsequent release (75%) at pH 6.75 in the distal duodenum after 4 to 5 hours, ensuring 24-hour coverage. Unlike other PPIs, dexlansoprazole's absorption isn't meal-dependent, offering flexibility in administration, potentially improving patient adherence and quality of life.

Comparing dexlansoprazole with esomeprazole, another PPI, reveals pharmacokinetic disparities. Esomeprazole, a delayed-release formulation, reaches peak plasma concentrations around 1.6 hours post-dose and requires administration at least an hour before meals for maximal efficacy. In contrast, dexlansoprazole modified-release can be taken irrespective of meals.

CLINICAL EVIDENCE

Clinical evidence supports dexlansoprazole's superiority over placebo in resolving GORD symptoms. A systematic review and meta-analysis revealed significant efficacy of dexlansoprazole across doses (30 mg, 60 mg, 90 mg) in improving heartburn, reflux, and related complications. Dexlansoprazole demonstrated superior symptom relief compared to placebo, leading to improved sleep quality, reduced symptom severity, and enhanced daily functioning.

Moreover, dexlansoprazole significantly increased 24-hour heartburn-free periods compared to placebo across various doses. Notably, while both 30 mg and 60 mg doses were effective, higher doses did not consistently provide added benefit, suggesting a need for dose optimisation based on individual response.

In a Phase 1 crossover study by Kukulka et al, comparing dexlansoprazole modified-release 60 mg and esomeprazole 40 mg effects on 24-hour intragastric pH in healthy adults, dexlansoprazole exhibited prolonged gastric acid control compared to esomeprazole.

Dexlansoprazole showed extended activity from 0 to 24 hours postdose, notably significant from 12 to 24 hours, while both drugs had similar effects from 0 to 12 hours postdose. Dexlansoprazole maintained intragastric pH above 4 for 58% of the time versus esomeprazole's 48%. Previous studies indicate similar results with dexlansoprazole and slightly lower percentages with esomeprazole.

Dexlansoprazole 60 mg notably outperformed esomeprazole 40 mg throughout the 24-hour period, primarily due to superior control from 12 to 24 hours postdose.

GASTRIC PH AND REFLUX DISEASE

Gastric pH, whether measured by time above pH 4.0 or median 24-hour pH, serves as the primary predictor of PPI efficacy in GORD patients. Intragastric pH monitoring in healthy individuals allows direct assessment of acid suppression, allowing for comparisons between antisecretory therapies and aiding clinicians in dose adjustments or agent switches.

In clinical trials, acid suppression is typically evaluated by mean pH or percentage of time pH exceeds 4, acting as a surrogate for GORD healing. A pH of 4 marks the threshold where refluxed gastric contents become harmful to the oesophagus. Studies in patients with erosive oesophagitis demonstrate that higher healing rates correlate with longer durations of intragastric pH above 4 over 24 hours.

PPIs are the most effective known agents for achieving this clinical target.

CONCLUSION

Dexlansoprazole, an isomer of lansoprazole, offers extended and flexible acid control, releasing in two pulses over 24 hours. Clinical evidence supports its superiority over placebo, enhancing symptom relief and increasing heartburn-free periods. Comparing dexlansoprazole with esomeprazole, meanwhile, reveals prolonged acid control on the part of dexlansoprazole.

Gastric pH, vital in GORD management, guides PPI efficacy assessment, with higher pH correlating with improved healing rates, and PPIs remain the most effective agents for achieving optimal pH levels. Among these, dexlansoprazole's unique formulation and clinical efficacy underscore its role in GORD management.

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REFERENCES

Armstrong, D, 2004. Review article: Gastric pH -- the most relevant predictor of benefit in reflux disease? Aliment Pharmacol Ther. 2004 Oct;20 Suppl 5:19-26.

Kirchheiner, J, et al, 2008. Relative potency of proton-pump inhibitors-comparison of effects on intragastric pH. European Journal of Clinical Pharmacology, 2008, 65 (1), pp.19-31.

Kukulka, M, et al, 2011. Comparator pH study to evaluate the single-dose pharmacodynamics of dual delayed-release dexlansoprazole 60 mg and delayed-release esomeprazole 40 mg. Clinical and Experimental Gastroenterology, 213-220.