Prokinetic effect of AS-4370 on gastric emptying in healthy adults

The effect of AS-4370 on gastric emptying was investigated in healthy adults using 99mTc-DTPA. Single doses of AS-4370 2.5, 5 or 10 mg or placebo were administered to 12 subjects in a controlled, double-blind, cross-over study. Tests were performed twice weekly in each subject. Thirty min after administration of test drug or placebo, each subject swallowed a bun and orange juice containing 200 microCi nuclide. The radioactivity of the gastric content was measured for 40 min and the activity of the residue was expressed as a percentage of count at the initiation of measurements. The percentage radioactivity, AUC and gastric emptying time fitted by a power exponential curve, were analyzed. No significant difference was observed between the three dose levels of AS-4370 and placebo in half emptying time. However, decreases in the percentage of radioactivity with time were noted; 5 mg at 10 to 16 min and 10 mg at 8 to 24 min after the start of recording. Lower AUCs after 5 mg and 10 mg compared to placebo were also found. The half emptying time was also shorter after 5 mg and 10 mg than placebo. There was no difference in these parameters between 2.5 mg and placebo. The results indicate that AS-4370 5 and 10 mg but not 2.5 mg accelerates gastric emptying in healthy adults.