Review article: pharmacological approaches to the optimal control of nocturnal intragastric acidity

Once daily, or even twice daily, dosing with proton-pump inhibitors does not reliably achieve optimal control of nocturnal intragastric acidity. The phenomenon of nocturnal acid breakthrough, defined as intragastric pH < 4 for more than 1 h in the overnight period, was initially described during twice daily dosing with proton-pump inhibitors and found to affect around 70% of individuals.

Given recent renewed interest in the potential consequences of nocturnal oesophageal acid exposure, it is appropriate to consider alternative pharmacological approaches to optimizing the control of nocturnal intragastric acidity.

Nocturnal acid control is considered to be the maintenance of intragastric pH > 4 for the duration of the night-time period. At pH > 4, gastric refluxate entering the oesophagus is non-caustic because pepsin is biologically inactive in this pH range.

Although conventional delayed-release proton-pump inhibitors effectively control daytime, food-stimulated gastric acid secretion, they allow recovery of acid secretion during the night. Bedtime administration of immediate-release omeprazole with sodium bicarbonate (Zegerid, Santarus, Inc., San Diego, CA, USA) has been shown to be highly effective in maintaining overnight intragastric pH above 4 for prolonged periods.

Pharmacodynamic studies in patients with gastro-oesophageal reflux disease have compared the effects of bedtime administration of immediate-release omeprazole, to either predinner or bedtime administration of three different delayed-release proton-pump inhibitors. Bedtime administration of immediate-release omeprazole was more effective at controlling overnight intragastric acidity than predinner administration of pantoprazole or bedtime administration of lansoprazole.