The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease

Background: Tegaserod (HTF 919), a 5-HT4 receptor partial agonist, has prok inetic effects that might be useful in decreasing acid reflux in gastro-oes ophageal reflux disease (GERD). Methods: To investigate the potential clinical utility of tegaserod in GERD , a five-period crossover study (balanced Latin square) was designed to eva luate the efficacy of 4 b.d. doses of tegaserod vs. placebo. Four-hour mano metry (1 h fasting and 3 h postprandial) with continuous recording of lower oesophageal sphincter pressure and distal oesophageal pH, was performed at the end of each 2-week treatment period in 19 patients with mild-to-modera te GERD. Recordings were scored for mean lower oesophageal sphincter pressu re, number of transient lower oesophageal sphincter relaxations, and distal oesophageal acid exposure. Results: Tegaserod (1 mg/day and 4 mg/day) caused a more than 50% decrease in acid exposure in the postprandial period in patients with abnormal acid exposure, although only the 1 mg/day tegaserod treatment elicited statistic ally significant decreasing (P < 0.05) for the entire treatment group (perc entage time for which pH < 4: placebo=13%; 1 mg/day dose=5%; 4 mg/day dose= 8%). A decreased number of reflux episodes was demonstrated with both the 1 mg/day and 4 mg/day tegaserod doses. There was no apparent effect on mean lower oesophageal sphincter pressure, whilst transient lower oesophageal sp hincter relaxations frequency decreased in the 1-2.5 h post-dose. Conclusions: Tegaserod in a dose of 1 mg/day causes a significant decrease in postprandial oesophageal acid exposure. The reduction in oesophageal aci d exposure with tegaserod treatment may result from enhanced oesophageal ac id clearance, improved gastric emptying, and/or reduced transient lower oes ophageal sphincter relaxations.