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

Authors


P. J.KahrilasDr Northwestern University Medical School, Division of Gastroenterology and Hepatology, Department of Medicine, Searle Building, 10th Floor, Suite 541, 303 East Chicago Avenue, Chicago, IL 60611, USA. E-mail: p_kahrilas@northwestern.edu

Abstract

Background:

Tegaserod (HTF 919), a 5-HT4 receptor partial agonist, has prokinetic effects that might be useful in decreasing acid reflux in gastro-oesophageal 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 evaluate the efficacy of 4 b.d. doses of tegaserod vs. placebo. Four-hour manometry (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-moderate GERD. Recordings were scored for mean lower oesophageal sphincter pressure, 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 statistically significant decreasing (P < 0.05) for the entire treatment group (percentage 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 sphincter 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 acid exposure with tegaserod treatment may result from enhanced oesophageal acid clearance, improved gastric emptying, and/or reduced transient lower oesophageal sphincter relaxations.

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