In this study, we examined the change of the intragastric pH after a single oral administration of omeprazole 20 mg plus mosapride 5 mg as compared with that following administration of omeprazole 20 mg alone in the early post-administration phase in H. pylori-negative subjects.
Mosapride citrate (mosapride) (4-amino-5-chloro-2-ethoxy-N-{[4-(4-fluorobenzyl)-2-morpholinyl]methyl}benzamide citrate) is a novel gastrokinetic agent that enhances gastrointestinal motility by stimulating the serotonin (5-HT4) receptor [4]. Mosapride stimulates acetylcholine release from the cholinergic nerve endings in the gastrointestinal wall and may enhance upper gastrointestinal motor activity in the postprandial state in conscious dogs [5]. After oral administration, mosapride is absorbed in the small intestine in rats, rather than in the stomach [6].
Mosapride accelerates gastric emptying in healthy adults. This study may indicate that mosapride accelerates the absorption of omeprazole. For example, mosapride accelerated the gastric emptying and completion rate of small bowel examinations in patients undergoing capsule endoscopy [7]. The gastric emptying time (GET) in the mosapride group was reduced and indicated the obvious effect of mosapride on the shortening of the GET. Moreover, preparation for barium enemas using mosapride before and after oral intestinal lavage solution (PEG-ELS) intake is more effective than the modified Brown's method that is commonly used in Japan [8]. Mosapride improves gastrointestinal motility and reduces gastric stasis or gastroesophageal reflux [9, 10]. Mosapride also alleviates gastrointestinal dysfunction.
Although many factors are implicated in the development of gastroesophageal reflux disease (GERD), acid reflux to the esophagus is considered to be the major cause of this disease. Treatment with PPIs to provide potent, long-term suppression of gastric acid is essential for disease management. On the other hand, the transient heartburn associated with mild GERD is attributed mainly to temporary, short-term gastric acid reflux. For example, water and antacid immediately increased the gastric pH, while PPIs showed a delayed, but prolonged effect as compared to H2RAs [11]. Therefore, rapid acid suppression is one of the most important factors for the resolution of these symptoms. Because administration of omeprazole plus mosapride promptly suppressed gastric acid secretion [12], it was originally considered to be a useful drug for on-demand treatment of mild GERD. Omeprazole used with mosapride may accelerate the onset of action, and may thus be more suitable for on-demand use than omeprazole alone. Furthermore, fixed mosapride-omeprazole combination therapy may be more useful than omeprazole alone.
If mosapride accelerates the absorption of omeprazole, why was the gastric pH not higher during 0-1, 1-2, or 2-3-hour period (Figure 2)? We suspect that mosapride has not so quick and strong effect for earlier phase of gastric emptying. If mosapride can accelerate gastric emptying quickly for 1 hour compare to control, earlier effect may be observed during 0-1 or 1-2 or 2-3 hour study period.
Intragastric pH during 3-4-hour study period was fallen (Figure 2). Why this transient decrease of intragastric pH observed using PPI? Because PPI can block only activated proton pomp, gastric pH does not reflect blood concentration of omeprazole directory. Our previous manuscripts [13–15] reported that after PPI administration, intragastric pH value raise showing up and down.
The limitations of the present study are: short time (6 hours) study period may be insufficient for the end of both mosapride's and omeprazole's effects for intragastric pH, and data were collected from healthy volunteers and not GERD patients requiring on-demand therapy. Further study may be necessary to evaluate these problems.
The ideal medication for the treatment of heartburn should have the rapid onset of action needed for on-demand treatment, as well as a sufficient duration of action to ensure that the symptoms are controlled. On the basis of our results, we conclude that omeprazole 20 mg plus mosapride 5 mg produced a rise in intragastric pH more promptly than omeprazole 20 mg alone in H. pylori-negative healthy male subjects. The clinical implications of our results remain unclear; however, our findings suggest that oral administration of the combination of omeprazole 20 mg preceded by mosapride 5 mg tablets may be suitable for on-demand treatment in patients with mild GERD. Further study may be necessary to evaluate the effects in GERD subjects.