Review article: putting immediate‐release proton‐pump inhibitors into clinical practice – improving nocturnal acid control and avoiding the possible complications of excessive acid exposure

Abstract

Summary Nocturnal gastro‐oesphageal reflux is an under‐appreciated clinical challenge. This condition may cause symptoms such as nocturnal heartburn, or it may be asymptomatic. In addition, patients may experience sleep disturbances that can potentially lead to complications such as erosive oesophagitis and Barrett's oesophagus, and may be a risk factor for development of oesophageal adenocarcinoma. Delayed‐release proton‐pump inhibitors (PPIs) have traditionally been effective in treating both daytime and night‐time reflux symptoms, but are limited in control of nocturnal acidity by their pharmacodynamic characteristics. This narrative review addresses the prevalence, impact and pharmacologic approaches used to control nocturnal acidity. Methods to optimize nocturnal acid control include careful attention to dosing schedule, using higher doses of PPIs, adding an histamine H2‐receptor antagonist at bedtime to once or twice daily delayed‐release PPI, or using immediate‐relase omeprazole (Zegerid powder for oral suspension; Santarus, Inc., San Diego, CA, USA). This new formulation appears to provide sustained control of intragastric pH at steady state, and when dosed at bedtime, and may be effective in improving control of nocturnal pH and treating night‐time GERD.

Determinants of Abnormal Supine Reflux in 24-Hour pH Recordings

“…Interestingly, PPIs taken twice daily give better nocturnal acid control than a double dose taken either with breakfast or with the evening meal [19]. Addition of H 2 receptor antagonists at bedtime can augment overnight pH control, however, tolerance develops rapidly in the majority of patients [18]. Good control of nocturnal symptoms is achieved with morning dosing of the longer-acting PPIs esomeprazole and pantoprazole [20,21], because they continue to work into the early nighttime period.…”

“…However, this is not as simple as it first seems. Proton pump inhibitors (PPIs), the most effective antireflux drugs, need to label active proton pumps so are best taken just before a meal [18]. Interestingly, PPIs taken twice daily give better nocturnal acid control than a double dose taken either with breakfast or with the evening meal [19].…”

Acid-Suppressive Effects of Various Regimens of Omeprazole in Helicobacter pylori-Negative CYP2C19 Homozygous Extensive Metabolizers: Which Regimen Has the Strongest Effect?

“…Therefore, inhibition of NAB can be considered one of the most important factors to consider during treatment with a PPI [10]. In the present study, in 4 of the 5 regimens, NAB occurred in all 7 subjects; whereas, with 20 mg bid it occurred in only 3.…”

“…In patients with high-grade GERD and Barrett esophagus, exposure of the esophagus to acid occurs frequently in the nighttime as well as daytime periods [8,9], and it is now considered that insufficient nocturnal acid-suppression is one of the causes of refractory GERD and the progression of Barrett esophagus [10]. Therefore, nocturnal gastric acid breakthrough (NAB), recovery of nocturnal gastric acid secretion in the overnight period during administration of a PPI [11,12], has drawn much attention.…”

Proton pump inhibitors in gastroesophageal reflux disease: a custom-tailored therapeutic regimen

“…The longer the plasma t½ is, the higher the AUC 0-24 value, and hence the antisecretory effect. Maintenance of intragastric pH > 3 is correlated to healing of duodenal ulcer, of intragastric pH > 4 to healing of gastric ulcer, and of intraesophageal pH > 4 to healing of erosive esophagitis (19)(20)(21). Lansoprazole, pantoprazole and rabeprazole have linear pharmacokinetics (correlation between C max and AUC 0-24 ), unlike omeprazole and esomeprazole (non-linear), which significantly inhibit CYP2C19 (22).…”