Published online Jul 21, 2013. doi: 10.3748/wjg.v19.i27.4380
Revised: May 10, 2013
Accepted: May 16, 2013
Published online: July 21, 2013
AIM: To evaluate the effects of DA-9701 on the gastric emptying of a solid meal using the 13C-octanoic acid breath test in a mouse model.
METHODS: Male C57BL/6 mice aged > 8 wk and with body weights of 20-25 g were used in this study. The solid test meal consisted of 200 mg of egg yolk labeled with 1.5 L/g 13C-octanoic acid. The mice were placed in a 130 mL chamber flushed with air at a flow speed of 200 mL/min. Breath samples were collected for 6 h. The half-emptying time and lag phase were calculated using a modified power exponential model. To assess the reproducibility of the 13C-octanoic acid breath test, the breath test was performed two times at intervals of one week in ten mice without drug treatment. To assess the gastrokinetic effects of DA-9701, the breath test was performed three times in another twelve mice, with a randomized crossover sequence of three drug treatments: DA-9701 3 mg/kg, erythromycin 6 mg/kg, or saline. Each breath test was performed at an interval of one week.
RESULTS: Repeatedly measured half gastric emptying time of ten mice without drug treatment showed 0.856 of the intraclass correlation coefficient for the half gastric emptying time (P = 0.004). The mean cumulative excretion curve for the 13C-octanoic acid breath test showed accelerated gastric emptying after DA-9701 treatment compared with the saline control (P = 0.028). The median half gastric emptying time after the DA-9701 treatment was significantly shorter than after the saline treatment [122.4 min (109.0-137.9 min) vs 134.5 min (128.4-167.0 min), respectively; P = 0.028] and similar to that after the erythromycin treatment [123.3 min (112.9-138.2 min)]. The lag phase, which was defined as the period taken to empty 15% of a meal, was significantly shorter after the DA-9701 treatment than after the saline treatment [48.1 min (44.6-57.1 min) vs 52.6 min (49.45-57.4 min), respectively; P = 0.049].
CONCLUSION: The novel prokinetic agent DA-9701 accelerated gastric emptying, assessed with repeated measurements in the same mouse using the 13C-octanoic acid breath test. Our findings suggest that DA-9701 has therapeutic potential for the treatment of functional dyspepsia.
Core tip: DA-9701 is a newly formulated prokinetic agent obtained from extracts of Pharbitis Semen and Corydalis Tuber. The 13C-octanoic acid breath test is a reliable and responsive method for measuring gastric emptying in small laboratory animal. This technique can be performed repeatedly in the same animal and reflect exact pharmacological effects without sacrifice of the animal. This study demonstrated the gastrokinetic effects of DA-9701, using repeated 13C-octanoic acid breath tests in the same animal. The gastrokinetic effect of DA-9701 could have therapeutic potential for the treatment of familial dysautonomia.