Effects of a new motilide, ABT-229, on gastric emptying and postprandial antroduodenal motility in healthy volunteers.
BACKGROUND
ABT-229 is a recently developed derivative of erythromycin, devoid of antibiotic activity. We studied the effect of ABT-229 on gastric emptying and postprandial antroduodenal motility in healthy volunteers.


METHODS
Placebo, 4 and 16 mg ABT-229 were given as a single oral dose to nine healthy volunteers, in a randomized, 3-period crossover design. A solid meal (250 kcal) was given twice, 45 min after drug ingestion and 4 h later. Gastric emptying of each meal was studied using the 13C-octanoic breath test. Antroduodenal motility was recorded during the total 9-h period.


RESULTS
After the first meal, both the 4 and 16 mg doses increased the gastric emptying rate to a similar extent. ABT-229 stimulated the contractile motility of the antrum dose-dependently. The half-emptying time and the lag-phase of gastric emptying correlated with the number of pressure waves that were propagated over the antrum and the mean amplitude of antral pressure waves. After the second meal no significant effects of ABT-229 were found.


CONCLUSIONS
A single dose of the new motilin agonist ABT-229 strongly increases the gastric emptying rate in healthy volunteers by increasing the strength and length of propagation of antral pressure waves. ABT-229 has the potential to become a new prokinetic drug.
Verhagen
M A
MA
Department of Gastroenterology, University Hospital, Utrecht, The Netherlands.
Samsom
M
M
Maes
B
B
Geypens
B J
BJ
Ghoos
Y F
YF
Smout
A J
AJ
D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects*; D004917:Erythromycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D008297:Male; D008365:Manometry; D009037:Motilin / Q000819:agonists; D019518:Postprandial Period; D012016:Reference Values
D005765:Gastrointestinal Agents; D009037:Motilin; C114264:Alemcinal; D004917:Erythromycin