Since 1984 many studies have described the effects of the macrolide antibiotic erythromycin on gastrointestinal motility. 1±3 Erythromycin was subsequently shown to be an agonist of the motilin receptor. 4 Motilin is a peptide gut hormone, which is produced in the duodenum and plays a role in the regulation of upper gastrointestinal motility. 5 In healthy humans, erythromycin induces contractions of the gastric antrum, enhances antropyloroduodenal co-ordination, induces antral phase III activity and enhances the tone of the gastric fundus. 6±12 In patients with diabetic or postvagotomy gastroparesis, erythromycin stimulates antral motility and normalizes gastric emptying. 3, 13±20 However, a major disadvantage of the use of erythromycin as a prokinetic drug is its antibacterial activity and the risk of inducing a resistant bacterial strain. Therefore, new erythromycin analogues have been developed, so-called motilides, which lack antibiotic activity. One of these, ABT-229 (8,9-anhydro-4¢¢-deoxy-3¢-N-desmethyl-3¢-N-ethylerythromycin B 6,9-hemiacetal), has a relatively high bioavailability after oral administration and strong prokinetic effects in vitro. 21 This study was designed to investigate the effects of two single oral doses (4 mg, 16 mg) of ABT-229 on the SUMMARY 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 13 C-octanoic breath test. Antroduodenal motility was recorded during the total 9-h period.