DOSE-RELATED EFFECTS OF N-DEMETHYL-N-ISOPROPYL-8,9-ANHYDROERYTHROMYCIN-A 6,9-HEMIACETAL ON GASTRIC-EMPTYING OF SOLIDS IN HEALTHY-HUMAN VOLUNTEERS

The purpose of our study was to evaluate the effects of a new nonantib iotic motilide derived from erythromycin, EM574, on gastric emptying a nd to evaluate its safety. Thirty healthy volunteers received one of f ive oral doses of EM574 (5, 10, 20, 30 mg and placebo) in a randomized , double-blind, five-period, cross-over design; each dosing period was separated by 1-wk washout. Gastric emptying was measured by C-13-octa noic acid breath test. A total of 10, 20, 30 mg of EM574 significantly accelerated both lag phase and gastric half-emptying time (P < .001) compared to placebo. The 5-mg dose of EM574 also significantly shorten ed the gastric half-emptying time (P < .05). Mean gastric half-emptyin g times were 173, 153, 147, 149 min with EM574 5, 10, 20, 30 mg, respe ctively (placebo, mean 189 min). EM574 accelerated gastric emptying in a dose-related manner (P < .001 for linear trend, P < .05 for quadrat ic trend). However, the 30-mg dose did not accelerate gastric emptying more than the 20-mg dose. EM574 was well tolerated; 7 of 56 participa nts receiving the 20- or 30-mg dose developed nausea, and only 2 of 28 receiving the 30-mg dose experienced vomiting. EM574 accelerates gast ric emptying in a dose-dependent manner with minimal side effects afte r a single administration of up to 20 mg. EM574 shows promise for trea tment of patients with impaired gastric emptying.