NIGHTTIME DOSING OF OMEPRAZOLE IMMEDIATE-RELEASE ORAL SUSPENSION RAPIDLY DECREASES NOCTURNAL GASTRIC ACIDITY

Abstract

Purpose: Proton pump inhibitors (PPIs) suppress gastric acid secretion sufficiently to treat most symptoms of GERD. However, in some patients, PPIs fail to control nighttime gastric acid secretion and also fail to control nighttime GERD symptoms. The PPIs used to treat these symptoms have all been delayed-release formulations with enteric coatings. A new omeprazole immediate-release suspension (OME-IR[SUSP]) has been developed, using sodium bicarbonate to protect the acid-labile PPI, rather than the traditional delayed-release enteric coating. The present trial was conducted to evaluate the effectiveness of OME-IR(SUSP) in controlling nighttime gastric acidity after twice-daily (b.i.d.) dosing. Methods: Seventeen healthy subjects were enrolled in this open-label trial. Single 20-mg doses of OME-IR(SUSP) (Santarus, San Diego) were given 1 hr prior to breakfast (qAM) for 7 days. On Day 8, the 20-mg suspension was given b.i.d.: at 0830 hrs (1 hr prior to a standardized high-fat breakfast) and at 2200 hrs (bedtime). On Days 7 and 8, standardized lunch and dinner were given at 1300 and 1800 hrs. Gastric pH was continuously monitored (Medtronic) for 24 hrs following the morning doses on Days 7 and 8. The percent time pH was >4 was assessed for the 8-hr nighttime period (2200-0600 hrs) and for the 24-hr period following the morning dose. The proportion of subjects with “nocturnal acid breakthrough” (NAB) (> 1 hr of continuous pH <4) was assessed for the 8-hr nighttime period. Results: The figure below displays the 24-hr median gastric pH profile at steady state for b.i.d. dosing of OME-IR 20 mg. After the bedtime dose, OME-IR 20 mg abruptly raised the gastric pH and sustained this effect for approximately 8 hrs. The median % time pH was >4 was greater for b.i.d dosing (87%) than for qAM dosing (39%) (p <0.001). NAB occurred in fewer subjects dosed b.i.d. (5/17 [29%]) than dosed qAM (13/17 [76%]) (p = 0.005).[figure 1]FigureConclusions: Twice-daily dosing (before breakfast and at bedtime) with OME-IR(SUSP) is effective in controlling nighttime acidity. Nighttime administration of OME-IR(SUSP) may be more effective in controlling nighttime GERD symptoms than delayed-release PPIs.