title: Effect of DA-9701 on gastric emptying in a mouse model: assessment by ¹³C-octanoic acid breath test.
abstract: OBJECTIVE
  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].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul 137-070, South Korea.
authors.forename: Chul-Hyun
authors.initials: CH
authors.lastname: Lim
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Choi
authors.forename: Hyeyeon
authors.initials: H
authors.lastname: Park
authors.forename: Myong Ki
authors.initials: MK
authors.lastname: Baeg
authors.forename: Jae Myung
authors.initials: JM
authors.lastname: Park
mesh_terms: D000818:Animals; D001835:Body Weight; D001944:Breath Tests; D002210:Caprylates / Q000737:chemistry; D002247:Carbon Isotopes / Q000737:chemistry; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004917:Erythromycin / Q000627:therapeutic use; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D028321:Plant Preparations / Q000627:therapeutic use*; D011897:Random Allocation; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D002210:Caprylates; D002247:Carbon Isotopes; C533973:DA-9701; D005765:Gastrointestinal Agents; D028321:Plant Preparations; D004917:Erythromycin; C031492:octanoic acid
keywords: Breath test; DA-9701; Functional dyspepsia; Gastric emptying; Prokinetic agent