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 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.
Kahrilas
P J
PJ
Northwestern University Medical School, Chicago, Illinois 60611, USA. p_kahrilas@northwestern.edu
Quigley
E M
EM
Castell
D O
DO
Spechler
S J
SJ
D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004943:Esophagogastric Junction / Q000187:drug effects*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008365:Manometry; D019518:Postprandial Period; D011312:Pressure; D016896:Treatment Outcome
D005765:Gastrointestinal Agents; D007211:Indoles; C105050:tegaserod