The effect of motilin agonist ABT-229 on gastro-oesophageal reflux, oesophageal motility and lower oesophageal sphincter characteristics in GERD patients.
BACKGROUND
ABT-229, a motilin agonist without antibacterial activity, has been shown to enhance both lower oesophageal sphincter pressure in cats and gastric emptying in humans.


OBJECTIVE
To investigate the effect of oral treatment with ABT-229 10 mg b.d., ABT-229 5 mg b. d. and cisapride 10 mg q.d.s. on gastro-oesophageal reflux, lower oesophageal sphincter pressure, transient lower oesophageal sphincter relaxations and symptoms in GERD patients.


METHODS
Twenty-four GERD patients completed the study. A randomized, double-blind, placebo-controlled, three-period incomplete crossover design was used with three dosing periods of 7 days. All patients received ABT-229 10 mg b.d. and placebo during two of the three periods. In the remaining period 12 patients were given ABT-229 5 mg b.d. and 12 received cisapride 10 mg q.d.s. Ambulatory 24 h recordings of oesophageal pH and pharyngeal, oesophageal, lower oesophageal sphincter and gastric pressures were performed on day 7 using an assembly incorporating a Dent sleeve connected to a portable water-perfused manometric system.


RESULTS
Oesophageal acid exposure was not affected by ABT-229 or cisapride, but the incidence of reflux episodes was reduced by cisapride. None of the drugs affected oesophageal motility, lower oesophageal sphincter pressure or the incidence of transient lower oesophageal sphincter relaxations. Both ABT-229 10 mg b.d. and cisapride reduced the severity of daytime heartburn.


CONCLUSIONS
The value of ABT-229 in the treatment of GERD appears to be limited.
Van Herwaarden
M A
MA
Gastrointestinal Research Unit, Department of Gastroenterology and Surgery, University Medical Center Utrecht, the Netherlands. m.herwaarden@digd.a2u.nl
Samsom
M
M
Van Nispen
C H
CH
Verlinden
M
M
Smout
A J
AJ
D000328:Adult; D020117:Cisapride / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004947:Esophagus / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009037:Motilin / Q000819:agonists*
D005765:Gastrointestinal Agents; D009037:Motilin; C114264:Alemcinal; D004917:Erythromycin; D020117:Cisapride