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

P. J. Kahrilas, E. M M Quigley, D. O. Castell, S. J. Spechler

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1503-1509
Number of pages7
JournalAlimentary Pharmacology and Therapeutics
Volume14
Issue number11
DOIs
StatePublished - 2000

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Esophageal Diseases
Gastroesophageal Reflux
Lower Esophageal Sphincter
Acids
Pressure
Placebos
Postprandial Period
Receptors, Serotonin, 5-HT4
tegaserod
Gastric Emptying
Manometry
Therapeutics
Cross-Over Studies
Fasting

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease. / Kahrilas, P. J.; Quigley, E. M M; Castell, D. O.; Spechler, S. J.

In: Alimentary Pharmacology and Therapeutics, Vol. 14, No. 11, 2000, p. 1503-1509.

Research output: Contribution to journalArticle

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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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