Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor - Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region

Abstract

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.

Keywords: Asia; Delayed-action preparations; Dexlansoprazole; Gastroesophageal reflux; Proton pump inhibitors.

Figure 1

Chemical structure of (A) dexlansoprazole (R-lansoprazole) and (B) lansoprazole. Dexlansoprazole is one of 2 stereoisomers that are mirror images of each other and are non-superimposable.

Figure 2

Mean plasma concentration-time profiles for dexlansopra-zole and lansoprazole in healthy participants (day 5). Adapted from Vakily et al with permission.

Figure 3

Mean dexlansoprazole plasma concentration-time profile for maximum concentration following administration of a single oral dose of dexlansoprazole 90 mg under fasted and various fed conditions. Reprinted from Lee et al with permission from John Wiley & Sons, Inc. © 2009 Takeda Global Research & Development Center, Inc.

Figure 4

Results on day 5 after daily oral doses of dexlansoprazole 60 mg given 30 minutes before meals or an evening snack. (A) Mean linear plasma concentration–time profiles and (B) mean intragastric pH measurements. On the 24-hour scale, the x-axis shows hour 8:00 on the morning of day 5 to hour 8:00 on day 6. Upward and downward pointing arrows indicate the beginning and end of the monitoring periods for each regimen, respectively. For the lunch, dinner and snack regimens, data after 8:00 hours on day 6 are transposed to the beginning of the chart so that the mean 24-hour pH profiles of all 4 regimens can be compared in a single 24-hour view that reflects the diurnal effect of treatment on pH. Reprinted from Lee et al with permission from John Wiley & Sons, Inc. ©2010 Takeda Global Research & Development Center, Inc.

Figure 5

Control of heartburn over 24 hours by dexlansoprazole versus placebo in patients with healed erosive esophagitis (intent to treat population). *P < 0.0025 vs placebo. Adapted from Metz et al With permission from John Wiley & Sons, Inc. © 2009 Takeda Global Research & Development Center, Inc.